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Bordetella pertussis

Table of Contents
  1. General Information
    1. NCBI Taxonomy ID
    2. Disease
    3. Introduction
    4. Microbial Pathogenesis
    5. Host Ranges and Animal Models
    6. Host Protective Immunity
  2. Vaccine Related Pathogen Genes
    1. TcfA (Other)
    2. brkA (Protective antigen)
    3. Cpn60 (Protective antigen)
    4. CyaA (Protective antigen)
    5. FhaB (Protective antigen)
    6. Prn (Protective antigen)
    7. PtxA (Protective antigen)
    8. PtxB (Protective antigen)
    9. PtxC (Protective antigen)
    10. PtxD (Protective antigen)
    11. PtxE (Protective antigen)
    12. S1 (Protective antigen)
    13. aroA (Virmugen)
    14. dnt (Virmugen)
  3. Vaccine Related Host Genes
    1. IgG
  4. Vaccine Information
    1. Actacel
    2. Adacel
    3. Adacel-Polio
    4. B. pertussis BrkA protein vaccine
    5. B. pertussis Cpn60 protein vaccine
    6. B. pertussis CyaA protein vaccine
    7. B. pertussis DNA vaccine encoding Prn
    8. B. pertussis DNA vaccine pcDNA/S1
    9. B. pertussis FhaB and 69 kDa OMP protein vaccine
    10. B. pertussis PTx protein vaccine
    11. Boostrix
    12. Boostrix-Polio
    13. Bordetella pertussis aroA mutant vaccine
    14. Bordetella pertussis BPZE vectored vaccine
    15. Bordetella pertussis dnt mutant vaccine
    16. DAPTACEL
    17. Infanrix
    18. Infanrix -IPV/Hib
    19. Infanrix-hexa
    20. Infanrix-IPV
    21. Infanrix/Hib
    22. KINRIX
    23. Pediacel
    24. Pediarix
    25. Pentacel
    26. Quadracel
    27. rBCG-S1PT
    28. S. gordonii-PT
    29. Tripacel
    30. Tripedia
    31. VC-TetC/Tcf
  5. References
I. General Information
1. NCBI Taxonomy ID:
520
2. Disease:
Whooping Cough
3. Introduction
Bordetella pertussis is a Gram-negative, aerobic coccobacillus of the genus Bordetella, and the causative agent of pertussis or whooping cough. Pertussis (or Whooping Cough), is an infection of the respiratory system and characterized by a “whooping” sound when the person breathes in. In the US it killed 5,000 to 10,000 people per year before a vaccine was available. Vaccination has transformed this and between 1985-88 fewer than 100 children died from pertussis. Worldwide in 2000, according to the WHO, around 39 million people were infected annually and about 297,000 died. Bordetella pertussis infects its host by colonizing lung epithelial cells. The infection occurs most with children under the age of one when they are unimmunized or children with faded immunity, normally around the age 11 through 18. The signs and symptoms are similar to a common cold: runny nose, sneezing, mild cough, and low-grade fever. The patient becomes most contagious during the catarrhal stage of infection, normally 2 weeks after the coughing begins. It may become airborne when the person coughs, sneezes, or laughs. Pertussis vaccine is part of the DTaP (diphtheria, tetanus, acellular pertussis) immunization. The paroxysmal cough precedes a crowing inspiratory sound characteristic of pertussis. After a spell, the patient might make a “whooping” sound when breathing in, or vomit. Adults have milder symptoms, like prolonged coughing without the “whoop.” Infants less than 6 months may not have the typical whoop. A coughing spell may last a minute or more, producing cyanosis, apnoea and seizures. However, when not in a coughing fit, the patient does not experience trouble breathing. This is because Bordetella pertussis inhibits the immune response and therefore very little mucus is generated in the lungs. A prolonged cough may be irritating and sometimes a disabling cough may go undiagnosed in adults for many months (Wiki: Bordetella pertussis).
4. Microbial Pathogenesis
The bacterium contains a surface protein, filamentous hemagglutinin, which binds to sulfatides that are found on cilia of epithelial cells. Once anchored, the bacterium produces tracheal cytotoxin, which stops the cilia from beating. This prevents the cilia from clearing debris from the lungs, so the body responds by sending the host into a coughing fit. These coughs expel some bacteria into the air, which are free to infect other hosts. Bordetella pertussis has the ability to inhibit the function of the host's immune system. Two toxins, known as the pertussis toxin (or PTx) and adenylate cyclase (CyaA), are responsible for this inhibition. CyaA converts ATP to cyclic AMP, and PTx inhibits an intracellular protein that regulates this process. The end result is that phagocytes convert too much ATP to cyclic AMP, which can cause disturbances in cellular signaling mechanisms, and prevent phagocytes from correctly responding to an infection (Wiki: Bordetella pertussis).
5. Host Ranges and Animal Models
Animal models of pertussis include primates, rats, mice, and rabbits (Salyers and Whitt., 2002).
6. Host Protective Immunity
Acellular pertussis vaccines are effective in providing immunity to whooping cough, by stimulating antibodies to pertussis toxins, as well as an adhesin (Salyers and Whitt., 2002).
1. aroA
  • Gene Name : aroA
  • NCBI Protein GI : 144037
  • Other Database IDs : CDD:179423
    CDD:30129
  • Taxonomy ID : 520
  • Gene Strand (Orientation) : ?
  • Protein Length : 442
  • Protein Note : 3-phosphoshikimate 1-carboxyvinyltransferase; Provisional
  • Protein Sequence : Show Sequence
    >gi|144037|gb|AAA22968.1| 5-enolpyruvylshikimate-3-phosphate synthase (EC 2.5.1.19) [Bordetella pertussis]
    MSGLAYLDLPAARLARGEVALPGSKSISNRVLLLAALAEGSTEITGLLDSDDTRVMLAALRQLGVSVGEV
    ADGCVTIEGVARFPTEQAELFLGNAGTAFRPLTAALALMGGDYRLSGVPRMHERPIGDLVDALRQFGAGI
    EYLGQAGYPPLRIGGGSIRVDGPVRVEGSVSSQFLTALLMAAPVLARRSGQDITIEVVGELISKPYIEIT
    LNLMARFGVSVRRDGWRAFTIARDAVYRGPGRMAIEGDASTASYFLALGAIGGGPVRVTGVGEDSIQGDV
    AFAATLAAMGADVRYGPGWIETRGVRVAEGGRLKAFDADFNLIPDAAMTAATLALYADGPCRLRNIGSWR
    VKETDRIHAMHTELEKLGAGVQSGADWLEVAPPEPGGWRDAHIGTWDDHRMAMCFLLAAFGPAAVRILDP
    GCVSKTFPDYFDVYAGLLAARD
  • Molecule Role : Virmugen
  • Molecule Role Annotation : An aroA mutant is highly attenuated in mice and induces significant protection from challenge with wild type B. pertussis (Roberts et al., 1990).
  • Related Vaccine(s): Bordetella pertussis aroA mutant vaccine
2. brkA
  • Gene Name : brkA
  • Sequence Strain (Species/Organism) : Bordetella pertussis
  • VO ID : VO_0011036
  • NCBI Protein GI : 562026
  • Other Database IDs : CDD:29328
    CDD:162346
    CDD:154874
  • Taxonomy ID : 520
  • Gene Strand (Orientation) : ?
  • Protein Name : BrkA
  • Protein pI : 7.12
  • Protein Weight : 95737.8
  • Protein Length : 1010
  • Protein Note : Pertactin-like passenger domains (virulence factors), C-terminal, subgroup 1, of autotransporter proteins of the type V secretion system of Gram-negative bacteria. This subgroup includes the passenger domains of Neisseria and Haemophilus IgA1 proteases...; cd01343
  • Protein Sequence : Show Sequence
    >gi|562026|gb|AAA51646.1| BrkA [Bordetella pertussis]
    MYLDRFRQCPSSLQIPRSAWRLHALAAALALAGMARLAPAAAQAPQPPVAGAPHAQDAGQEGEFDHRDNT
    LIAVFDDGVGINLDDDPDELGETAPPTLKDIHISVEHKNPMSKPAIGVRVSGAGRALTLAGSTIDATEGG
    IPAVVRRGGTLELDGVTVAGGEGMEPMTVSDAGSRLSVRGGVLGGEAPGVGLVRAAQGGQASIIDATLQS
    ILGPALIADGGSISVAGGSIDMDMGPGFPPPPPPLPGAPLAAHPPLDRVAAVHAGQDGKVTLREVALRAH
    GPQATGVYAYMPGSEITLQGGTVSVQGDDGAGVVAGAGLLDALPPGGTVRLDGTTVSTDGANTDAVLVRG
    DAARAEVVNTVLRTAKSLAAGVSAQHGGRVTLRQTRIETAGAGAEGISVLGFEPQSGSGPASVDMQGGSI
    TTTGNRAAGIALTHGSARLEGVAVRAEGSGSSAAQLANGTLVVSAGSLASAQSGAISVTDTPLKLMPGAL
    ASSTVSVRLTDGATAQGGNGVFLQQHSTIPVAVALESGALARGDIVADGNKPLDAGISLSVASGAAWHGA
    TQVLQSATLGKGGTWVVNADSRVQDMSMRGGRVEFQAPAPEASYKTLTLQTLDGNGVFVLNTNVAAGQND
    QLRVTGRADGQHRVLVRNAGGEADSRGARLGLVHTQGQGNATFRLANVGKAVDLGTWRYSLAEDPKTHVW
    SLQRAGQALSGAANAAVNAADLSSIALAESNALDKRLGELRLRADAGGPWARTFSERQQISNRHARAYDQ
    TVSGLEIGLDRGWSASGGRWYAGGLLGYTYADRTYPGDGGGKVKGLHVGGYAAYVGDGGYYLDTVLRLGR
    YDQQYNIAGTDGGRVTADYRTSGAAWSLEGGRRFELPNDWFAEPQAEVMLWRTSGKRYRASNGLRVKVDA
    NTATLGRLGLRFGRRIALAGGNIVQPYARLGWTQEFKSTGDVRTNGIGHAGAGRHGRVELGAGVDAALGK
    GHNLYASYEYAAGDRINIPWSFHAGYRYSF
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : A soluble fraction obtained from Bordetella pertussis was evaluated as adjuvant for the pertussis component of the Diphtheria-Pertussis-Tetanus (DPT) vaccine. High levels of antibodies were induced, and a 78% protection rate of mice challenged with live B. pertussis was observed. Two proteins were identified as the 73 kDa N-terminal alpha-domain of BrkA autotransporter protein and the Cpn60/60 kDa chaperonin. Both stimulated antibodies against pertussis and induced a 42% protection rate against the challenge (Cainelli et al., 2007).
  • Related Vaccine(s): B. pertussis BrkA protein vaccine
3. Cpn60
  • Gene Name : Cpn60
  • Sequence Strain (Species/Organism) : Bordetella pertussis
  • VO ID : VO_0011035
  • NCBI Protein GI : 968920
  • Other Database IDs : CDD:171768
    CDD:48161
  • Taxonomy ID : 520
  • Gene Strand (Orientation) : ?
  • Protein Name : Cpn60 (GroEL)
  • Protein pI : 4.85
  • Protein Weight : 51530.28
  • Protein Length : 547
  • Protein Note : chaperonin GroEL; Reviewed; PRK12849
  • Protein Sequence : Show Sequence
    >gi|968920|gb|AAA74967.1| Cpn60 (GroEL) [Bordetella pertussis]
    MAAKQVLFADEARVRIVRGVNVLANAVKTTLGPKGRNVVLERSFGAPTVTKDGVSVAKEIELKDKFENIG
    AQLVKDVASKTSDNAGDGTTTATVLAQAVVQEGLKYVAAGFNPIDLKRGIDKAVAAAVEELKKLSKPVTT
    SKEIAQVGSISANSDASIGQIIADAMDKVGKEGVITVEDGKSLENELDVVEGMQFDRGYLSPYFINSPEK
    QVAALDDPYVLIYDKKVSNIRDLLPVLEQVAKSSRPLLIIAEDVEGEALATLVVNNIRGILKTTAVKAPG
    FGDRRKAMLEDIAILTGGTVISEETGMSLEKATLQDLGQAKRIEVAKENTTIIDGAGDGKSIEARVKQIR
    AQIEEATSDYDREKLQERVAKLAGGVAVIRVGAATEVEMKEKKARVEDALHATRAAVEEGVVPGGGVALL
    RAKQAITGLKGDTADQNAGIKLILRAVEEPLRTIVTNAGDEASVVVNTVLNGKGNYGYNAATGEYGDLVE
    QGVLDPTKVTRTALQNAASVASLLLTAEAAVVELMENKPAAAPAMPGGMGGMGGMDF
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : A soluble fraction obtained from Bordetella pertussis was evaluated as adjuvant for the pertussis component of the Diphtheria-Pertussis-Tetanus (DPT) vaccine. High levels of antibodies were induced, and a 78% protection rate of mice challenged with live B. pertussis was observed. Two proteins were identified as the 73 kDa N-terminal alpha-domain of BrkA autotransporter protein and the Cpn60/60 kDa chaperonin. Both stimulated antibodies against pertussis and induced a 42% protection rate against the challenge (Cainelli et al., 2007).
  • Related Vaccine(s): B. pertussis Cpn60 protein vaccine
4. CyaA
  • Gene Name : CyaA
  • Sequence Strain (Species/Organism) : Bordetella pertussis
  • VO ID : VO_0011031
  • NCBI Protein GI : 580668
  • 3D structure: PDB ID : 2COL
  • Other Database IDs : CDD:146244
    CDD:111291
    CDD:164328
    GOA:P15318
    UniProtKB/UniProt: P15318
  • Taxonomy ID : 520
  • Gene Strand (Orientation) : ?
  • Protein Name : adenylate cyclase
  • Protein Length : 1706
  • Protein Note : Anthrax toxin LF subunit; pfam03497
  • Protein Sequence : Show Sequence
    >gi|580668|emb|CAA01202.1| adenylate cyclase [Bordetella pertussis]
    MQQSHQAGYANAADRESGIPAAVLDGIKAVAKEKNATLMFRLVNPHSTSLIAEGVATKGLGVHAKSSDWG
    LQAGYIPVNPNLSKLFGRAPEVIARADNDVNSSLAHGHTAVDLTLSKERLDYLRQAGLVTGMADGVVASN
    HAGYEQFEFRVKETSDGRYAVQYRRKGGDDFEAVKVIGNAAGIPLTADIDMFAIMPHLSNFRDSARSSVT
    SGDSVTDYLARTRRAASEATGGLDRERIDLLWKIARAGARSAVGTEARRQFRYDGDMNIGVITDFELEVR
    NALNRRAHAVGAQDVVQHGTEQNNPFPEADEKIFVVSATGESQMLTRGQLKEYIGQQRGEGYVFYENRAY
    GVAGKSLFDDGLGAAPGVPSGRSKFSPDVLETVPASPGLRRPSLGAVERQDSGYDSLDGVGSRSFSLGEV
    SDMAAVEAAELEMTRQVLHAGARQDDAEPGVSGASAHWGQRALQGAQAVAAAQRLVHAIALMTQFGRAGS
    TNTPQEAASLSAAVFGLGEASSAVAETVSGFFRGSSRWAGGFGVAGGAMALGGGIAAAVGAGMSLTDDAP
    AGQKAAAGAEIALQLTGGTVELASSIALALAAARGVTSGLQVAGASAGAAAGALAAALSPMEIYGLVQQS
    HYADQLDKLAQESSAYGYEGDALLAQLYRDKTAAEGAVAGVSAVLSTVGAAVSIAAAASVVGAPVAVVTS
    LLTGALNGILRGVQQPIIEKLANDYARKIDELGGPQAYFEKNLQARHEQLANSDGLRKMLADLQAGWNAS
    SVIGVQTTEISKSALELAAITGNADNLKSVDVFVDRFVQGERVAGQPVVLDVAAGGIDIASRKGERPALT
    FITPLAAPGEEQRRRTKTGKSEFTTFVEIVGKQDRWRIRDGAADTTIDLAKVVSQLVDANGVLKHSIKLD
    VIGGDGDDVVLANASRIHYDGGAGTNTVSYAALGRQDSITVSADGERFNVRKQLNNANVYREGVATQTTA
    YGKRTENVQYRHVELARVGQVVEVDTLEHVQHIIGGAGNDSITGNAHDNFLAGGSGDDRLDGGAGNDTLV
    GGEGQNTVIGGAGDDVFLQDLGVWSNQLDGGAGVDTVKYNVHQPSEERLERMGDTGIHADLQKGTVEKWP
    ALNLFSVDHVKNIENLHGSRLNDRIAGDDQDNELWGHDGNDTIRGRGGDDILRGGLGLDTLYGEDGNDIF
    LQDDETVSDDIDGGAGLDTVDYSAMIHPGRIVAPHEYGFGIEADLSREWVRKASALGVDYYDNVRNVENV
    IGTSMKDVLIGDAQANTLMGQGGDDTVRGGDGDDLLFGGDGNDMLYGDAGNDTLYGGLGDDTLEGGAGND
    WFGQTQAREHDVLRGGDGVDTVDYSQTGAHAGIAAGRIGLGILADLGAGRVDKLGEAGSSAYDTVSGIEN
    VVGTELADRITGDAQANVLRGAGGADVLAGGEGDDVLLGGDGDDQLSGDAGRDRLYGEAGDDWFFQDAAN
    AGNLLDGGDGRDTVDFSGPGRGLDAGAKGVFLSLGKGFASLMDEPETSNVLRNIENAVGSARDDVLIGDA
    GANVLNGLAGNDVLSGGAGDDVLLGDEGSDLLSGDAGNDDLFGGQGDDTYLFGVGYGHDTIYESGGGHDT
    IRINAGADQLWFARQGNDLEIRILGTDDALTVHDWYRDADHRVEIIHAANQAVDQAGIEKLVEAMAQYPD
    PGAAAAAPPAARVPDTLMQSLAVNWR
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : A study demonstrated that passive immunization with specific anti-B. pertussis adenylate cyclase antibodies or active immunization with purified B. pertussis secreted adenylate cyclase (cyaA) protect mice against a lethal respiratory challenge with B. pertussis or B. parapertussis. Results suggest that adenylate cyclase might be the primary cytotoxin responsible for mouse pulmonary lesions during respiratory tract infection with B. pertussis or with the related species B. parapertussis and is a protective antigen of B. pertussis (Guiso et al., 1989).
  • Related Vaccine(s): B. pertussis CyaA protein vaccine
5. dnt
  • Gene Name : dnt
  • Sequence Strain (Species/Organism) : Bordetella pertussis Tohama I
  • NCBI Gene ID : 2666936
  • NCBI Protein GI : 33594321
  • Locus Tag : BP3439
  • Genbank Accession : BX640421
  • Protein Accession : NP_881965
  • Taxonomy ID : 257313
  • Gene Starting Position : 3647083
  • Gene Ending Position : 3651477
  • Gene Strand (Orientation) : +
  • Protein Name : dermonecrotic toxin
  • Protein pI : 6.49
  • Protein Weight : 150126.42
  • Protein Length : 1464
  • Protein Note : Previously sequenced as Bordetella pertussis dermonecrotic toxin Dnt TR:Q45336 (EMBL: U10527) (1451 aa) fasta scores: E(): 0, 100% id in 1451 aa. Almost identical to Bordetella bronchiseptica dermonecrotizing toxin TR:Q9S5D5 (EMBL: AB020025) (1464 aa) fasta scores: E(): 0, 98.97% id in 1464 aa
  • DNA Sequence : Show Sequence
    >gi|33591275:3647083-3651477 Bordetella pertussis Tohama I, complete genome
    CGTGGATAAAGATGAATCGGCATTGCGGCAACTTGTCGACATGGCGCTTGTAGGCTACGACGGCGTGGTG
    GAAGAGTTGCTGGCGCTGCCCTCGGAAGAGTCCGGGGATCTTGCGGGTGGACGGGCCAAACGAGAGAAGG
    CCGAATTCGCGCTGTTTAGCGAAGCGCCCAACGGGGATGAACCCATCGGCCAGGATGCTCGTACATGGTT
    CTATTTTCCCAAGTACCGCCCGGTGGCGGTTTCCAATTTGAAGAAAATGCAGGTGGCGATTCGTGCTCGT
    CTCGAGCCTGAGTCATTGATCCTGCAGTGGTTGATCGCACTCGATGTCTATCTCGGCGTGTTGATCGCCG
    CCTTGTCCCGCACTGTGATCAGCGACCTGGTATTCGAGTATGTCAAGGCGCGCTACGAGATCTACTACCT
    ACTGAATCGCGTGCCGCATCCGCTGGCGACGGCGTACCTCAAGCGCCGCCGCCAGCGTCCGGTGGATCGT
    TCGGGACGTCTGGGCTCGGTGTTCGAACACCCGCTATGGTTCGCCTACGACGAATTGGCCGGCACCGTCG
    ATCTGGATGCCGACATCTACGAGCAGGCGCTCGCCGAAAGCATCGAACGCCGCATGGACGGAGAGCCGGA
    CGACGGCAGTCTGGATACCGCCGAACACGACGTATGGCGTTTGTGCCGCGACGGCATCAATCGGGGCGAG
    CAGGCGATTTTCCAGGCATCCGGCCCATATGGCGTGGTCGCGGATGCAGGGTATATGCGCACCGTTGCCG
    ATCTGGCGTATGCCGATGCATTGGCGGATTGCCTGCATGCCCAACTGCGCATCCGGGCGCAAGGCTCGGT
    CGATAGCCCGGGAGACGAGATGCCACGCAAACTTGATGCGTGGGAAATCGCCAAGTTTCATCTGGCCGCG
    ACCCAGCAGGCGCGGGTTGATCTGCTCGAGGCGGCGTTCGCGCTCGACTACGCCGCCTTGCGCGATGTGC
    GCGTCTACGGCGATTACCGCAATGCGCTGGCTCTTCGGTTCATCAAGCGCGAGGCCTTGCGGTTGCTGGG
    GGCGCGGCGCGGCAACGCCTCTACGATGCCGGCGGTTGCGGCTGGCGAGTACGACGAAATCGTGGCCAGT
    GGAGCAGCCAATGACGCGGCTTATGTATCCATGGCCGCCGCGTTGATCGCGGGCGTGCTCTGCGATCTCG
    AGAGCGCGCAGCGCACGTTGCCCGTCGTATTGGCCAGGTTTCGGCCCCTTGGCGTGCTTGCGCGATTCAG
    AAGGCTGGAGCAGGAAACCGCGGGCATGCTGCTTGGCGACCAGGAGCCGGAGCCTCGGGGCTTCATCAGT
    TTTACCGATTTTCGCGATAGCGACGCGTTCGCCAGCTACGCGGAGTATGCGGCCCAGTTCAACGACTATA
    TCGATCAATACAGCATACTCGAGGCGCAGCGGCTGGCGCGGATTCTGGCCCTGGGCTCGCGGATGACGGT
    CGATCAATGGTGCCTTCCCCTGCAGAAAGTACGGCACTACAAGGTGCTGACATCGCAGCCAGGGCTGATC
    GCGCGTGGAATCGAAAATCACAACAGGGGCATTGAATATTGCCTGGGGCGGCCGCCGCTGACCGATCTGC
    CGGGTCTTTTCACCATGTTCCAGCTCCATGATTCCAGCTGGCTGTTGGTATCGAACATCAACGGTGAGCT
    TTGGTCTGATGTCCTTGCGAACGCTGAGGTGATGCAGAATCCTACGCTGGCCGCCCTTGCCGAGCCGCAA
    GGCCGCTTTCGAACCGGCCGTCGAACGGGCGGGTGGTTTCTCGGCGGCCCCGCGACTGAAGGGCCAAGTC
    TGCGCGACAACTACCTCCTCAAATTGAGGCAGAGCAATCCGGGGCTGGATGTCAAGAAATGCTGGTATTT
    CGGGTATCGGCAAGAGTACAGGCTGCCCGCAGGCGCGCTGGGTGTGCCGCTATTCGCTGTTTCCGTTGCC
    CTGAGGCACAGTCTGGACGACCTCGCGGCGCACGCGAAGTCCGCTTTGTACAAACCCAGCGAATGGCAGA
    AGTTCGCCTTCTGGATCGTGCCGTTCTACCGGGAAATATTCTTTTCGACCCAGGATCGTTCCTATCGGGT
    CGATGTGGGGAGCATCGTCTTTGATTCGATTTCCTTGCTTGCCTCGGTGTTCAGCATAGGAGGGAAGTTG
    GGCAGTTTCACCCGTACCCAGTATGGCAACCTGCGCAATTTCGTGGTGCGGCAACGCATCGCGGGGTTGA
    GCGGGCAGCGCTTGTGGCGTTCGGTGCTCAAGGAGCTTCCGGCATTGATCGGAGCCAGCGGGTTGCGCCT
    GTCGCGTTCGCTGCTCGTCGATCTGTATGAGATCTTCGAGCCCGTGCCTATCCGTCGGCTTGTCGCGGGA
    TTCGTGAGCGCCACTACGGTCGGCGGGCGTAACCAGGCCTTCCTGCGGCAGGCATTCTCCGCTGCCAGTT
    CCTCGGCCGGGCGCACGGGGGGCCAATTGGCAAGCGAATGGCGGATGGCCGGCGTGGACGCCACCGGTTT
    GGTCGAGTCCACGTCGGGCGGCAGGTTTGAGGGCATCTACACGCGCGGCTTGGGACCGTTGAGCGAGTGC
    ACCGAGCACTTCATCGTCGAATCCGGGAATGCCTACAGAGTCATCTGGGATGCATACACGCATGGTTGGC
    GCGTGGTCAATGGGCGTTTGCCGCCGAGGCTGACCTATACCGTTCCGGTTCGGCTGAACGGGCAAGGCCA
    CTGGGAGACGCATCTGGATGTCCCTGGCCGGGGTGGGGCGCCGGAAATCTTCGGACGCATCCGCACGCGT
    AATCTGGTCGCCCTTGCCGCCGAGCAGGCCGCGCCGATGCGCCGCCTGCTCAACCAGGCGAGGCGTGTGG
    CGCTCAGGCATATCGATACCTGCAGGAGCAGGCTTGCGTTGCCGCGCGCTGAATCCGATATGGACGCGGC
    GATCCGGATTTTCTTCGGAGAGCCGGACGCCGGCCTTCGCCAGCGCATCGGGCGACGCCTGCAGGAGGTC
    AGGGCCTATATCGGCGATCTGAGTCCGGTCAATGACGTGCTGTACCGGGCGGGATATGACCTCGACGATG
    TCGCAACGCTGTTTAACGCAGTGGACCGGAACACGTCGCTGGGCAGGCAGGCTCGGATGGAGTTGTATCT
    GGATGCCATTGTCGATTTGCATGCCAGGCTCGGCTATGAAAATGCGCGTTTTGTCGACCTGATGGCGTTC
    CACCTGCTCAGCCTGGGCCATGCCGCGACGGCCAGTGAGGTCGTGGAGGCCGTTTCGCCCCGGCTGCTGG
    GCAATGTGTTCGATATCTCGAACGTCGCCCAGCTCGAACGCGGTATCGGGAATCCCGCCAGCACCGGTCT
    TTTCGTCATGCTGGGCGCCTATTCGGAATCGTCGCCCGCGATATTCCAGTCGTTCGTGAACGATATATTT
    CCCGCATGGCGACAGGCTTCCGGCGGGGGGCCGCTGGTATGGAACTTCGGTCCTGCCGCCATCAGCCCGA
    CGCGCCTGGATTACGCAAATACCGATATCGGATTGCTCAACCATGGGGATATTTCCCCGCTGCGCGCCAG
    GCCGCCATTGGGCGGCAGGCGCGACATCGATCTTCCTCCGGGGCTGGATATTTCGTTCGTGCGTTACGAC
    CGCCCGGTGCGCATGTCCGCGCCGCGTGCGCTCGACGCCAGCGTCTTCAGGCCGGTCGACGGGCCTGTCC
    ATGGCTATATTCAATCGTGGACGGGGGCTGAGATCGAATATGCGTACGGCGCGCCCGCAGCGGCACGCGA
    GGTCATGCTGACCGACAATGTGCGGATCATCAGCATCGAGAACGGCGATGAAGGGGCGATCGGGGTGCGC
    GTGAGGCTCGACACTGTTCCCGTCGCGACGCCGCTCATCCTGACTGGCGGCTCCTTGAGCGGGTGCACGA
    CGATGGTTGGGGTCAAGGAGGGCTACCTGGCCTTCTACCACACTGGCAAGTCGACCGAACTCGGGGATTG
    GGCGACTGCGCGCGAAGGCGTACAGGCGCTTTACCAGGCCCATTTGGCGATGGGGTACGCGCCGATCTCA
    ATCCCGGCGCCGATGCGCAATGACGACTTGGTCAGCATCGCCGCGACCTACGACCGGGCGGTCATTGCCT
    ATCTGGGCAAGGATGTGCCGGGAGGCGGCAGTACGCGCATAACGCGTCACGATGAGGGGGCGGGCAGTGT
    GGTTTCGTTCGACTACAACGCAGCAGTCCAGGCGTCGGCCGTTCCCCGCCTCGGCCAGGTATACGTTCTG
    ATTTCCAACGACGGACAAGGGGCGCGAGCCGTCCTGCTGGCGGAGGATCTGGCCTGGGCAGGCAGCGGCA
    GTGCCTTGGATGTGTTGAACGAACGATTGGTGACGTTGTTTCCGGCGCCGGTCTG
  • Protein Sequence : Show Sequence
    >gi|33594321|ref|NP_881965.1| dermonecrotic toxin [Bordetella pertussis Tohama I]
    MDKDESALRQLVDMALVGYDGVVEELLALPSEESGDLAGGRAKREKAEFALFSEAPNGDEPIGQDARTWF
    YFPKYRPVAVSNLKKMQVAIRARLEPESLILQWLIALDVYLGVLIAALSRTVISDLVFEYVKARYEIYYL
    LNRVPHPLATAYLKRRRQRPVDRSGRLGSVFEHPLWFAYDELAGTVDLDADIYEQALAESIERRMDGEPD
    DGSLDTAEHDVWRLCRDGINRGEQAIFQASGPYGVVADAGYMRTVADLAYADALADCLHAQLRIRAQGSV
    DSPGDEMPRKLDAWEIAKFHLAATQQARVDLLEAAFALDYAALRDVRVYGDYRNALALRFIKREALRLLG
    ARRGNASTMPAVAAGEYDEIVASGAANDAAYVSMAAALIAGVLCDLESAQRTLPVVLARFRPLGVLARFR
    RLEQETAGMLLGDQEPEPRGFISFTDFRDSDAFASYAEYAAQFNDYIDQYSILEAQRLARILALGSRMTV
    DQWCLPLQKVRHYKVLTSQPGLIARGIENHNRGIEYCLGRPPLTDLPGLFTMFQLHDSSWLLVSNINGEL
    WSDVLANAEVMQNPTLAALAEPQGRFRTGRRTGGWFLGGPATEGPSLRDNYLLKLRQSNPGLDVKKCWYF
    GYRQEYRLPAGALGVPLFAVSVALRHSLDDLAAHAKSALYKPSEWQKFAFWIVPFYREIFFSTQDRSYRV
    DVGSIVFDSISLLASVFSIGGKLGSFTRTQYGNLRNFVVRQRIAGLSGQRLWRSVLKELPALIGASGLRL
    SRSLLVDLYEIFEPVPIRRLVAGFVSATTVGGRNQAFLRQAFSAASSSAGRTGGQLASEWRMAGVDATGL
    VESTSGGRFEGIYTRGLGPLSECTEHFIVESGNAYRVIWDAYTHGWRVVNGRLPPRLTYTVPVRLNGQGH
    WETHLDVPGRGGAPEIFGRIRTRNLVALAAEQAAPMRRLLNQARRVALRHIDTCRSRLALPRAESDMDAA
    IRIFFGEPDAGLRQRIGRRLQEVRAYIGDLSPVNDVLYRAGYDLDDVATLFNAVDRNTSLGRQARMELYL
    DAIVDLHARLGYENARFVDLMAFHLLSLGHAATASEVVEAVSPRLLGNVFDISNVAQLERGIGNPASTGL
    FVMLGAYSESSPAIFQSFVNDIFPAWRQASGGGPLVWNFGPAAISPTRLDYANTDIGLLNHGDISPLRAR
    PPLGGRRDIDLPPGLDISFVRYDRPVRMSAPRALDASVFRPVDGPVHGYIQSWTGAEIEYAYGAPAAARE
    VMLTDNVRIISIENGDEGAIGVRVRLDTVPVATPLILTGGSLSGCTTMVGVKEGYLAFYHTGKSTELGDW
    ATAREGVQALYQAHLAMGYAPISIPAPMRNDDLVSIAATYDRAVIAYLGKDVPGGGSTRITRHDEGAGSV
    VSFDYNAAVQASAVPRLGQVYVLISNDGQGARAVLLAEDLAWAGSGSALDVLNERLVTLFPAPV
  • Molecule Role : Virmugen
  • Molecule Role Annotation : A live attenuated B. pertussis vaccine strain BPZE1 that protects mice upon a single intranasal administration was developed by deleting dnt gene (Feunou et al., 2008).
  • Related Vaccine(s): Bordetella pertussis dnt mutant vaccine
6. FhaB
  • Gene Name : FhaB
  • Sequence Strain (Species/Organism) : Bordetella pertussis
  • VO ID : VO_0011030
  • NCBI Protein GI : 3980256
  • 3D structure: PDB ID : 1RWR
  • Other Database IDs : CDD:141881
    GOA:Q45365
    HSSP: P12255
    InterPro: IPR008619
    InterPro: IPR008638
    InterPro: IPR010069
    UniProtKB/TrEMBL: Q45365
  • Taxonomy ID : 520
  • Gene Strand (Orientation) : ?
  • Protein Name : filamentous hemagglutinin
  • Protein pI : 9.35
  • Protein Weight : 332802.28
  • Protein Length : 3590
  • Protein Note : haemagglutination activity domain; cl05436
  • Protein Sequence : Show Sequence
    >gi|3980256|emb|CAA36409.1| filamentous hemagglutinin [Bordetella pertussis]
    MNTNLYRLVFSHVRGMLVPVSEHCTVGNTFCGRTRGQARSGARATSLSVAPNALAWALMLACTGLPLVTH
    AQGLVPQGQTQVLQGGNKVPVVNIADPNSGGVSHNKFQQFNVANPGVVFNNGLTDGVSRIGGALTKNPNL
    TRQASAILAEVTDTSPSRLAGTLEVYGKGADLIIANPNGISVNGLSTLNASNLTLTTGRPSVNGGRIGLD
    VQQGTVTIERGGVNATGLGYFDVVARLVKLQGAVSSKQGKPLADIAVVAGANRYDHATRRATPIAAGARG
    AAAGAYAIDGTAAGAMYGKHITLVSSDSGLGVRQLGSLSSPSAITVSSQGEIALGDATVQRGPLSLKGAG
    VVSAGKLASGGGAVNVAGGGAVKIASASSVGNLAVQGGGKVQATLLNAGGTLLVSGRQAVQLGAASSRQA
    LSVNAGGALKADKLSATRRVDVDGKQAVALGSASSNALSVRAGGALKAGKLSATGRLDVDGKQAVTLGSV
    ASDGALSVSAGGNLRANELVSSAQLEVRGQREVALDDASSARGMTVVAAGALAARNLQSKGAIGVQGGEA
    VSVANANSDAELRVRGRGQVDLHDLSAARGADISGEGRVNIGRARSDSDVKVSAHGALSIDSMTALGAIG
    VQAGGSVSAKDMRSRGAVTVSGGGAVNLGDVQSDGQVRATSAGAMTVRDVAAAADLALQAGDALQAGFLK
    SAGAMTVNGRDAVRLDGAHAGGQLRVSSDGQAALGSLAAKGELTVSAARAATVAELKSLDNISVTGGERV
    SVQSVNSASRVAISAHGALDVGKVSAKSGIGLEGWGAVGADSLGSDGAISVSGRDAVRVDQARSLADISL
    GAEGGATLGAVEAAGSIDVRGGSTVAANSLHANRDVRVSGKDAVRVTAATSGGGLHVSSGRQLDLGAVQA
    RGALALDGGAGVALQSAKASGTLHVQGGEHLDLGTLAAVGAVDVNGTGDVRVAKLVSDAGADLQAGRSMT
    LGIVDTTGDLQARAQQKLELGSVKSDGGLQAAAGGALSLAAAEVAGALELSGQGVTVDRASASRARIDST
    GSVGIGALKAGAVEAASPRRARRALRQDFFTPGSVVVRAQGNVTVGRGDPHQGVLAQGDIIMDAKGGTLL
    LRNDALTENGTVTISADSAVLEHSTIESKISQSVLAAKGDKGKPAVSVKVAKKLFLNGTLRAVNDNNETM
    SGRQIDVVDGRPQITDAVTGEARKDESVVSDAALVADGGPIVVEAGELVSHAGGIGNGRNKENGASVTVR
    TTGNLVNKGYISAGKQGVLEVGGALTNEFLVGSDGTQRIEAQRIENRGTFQSQAPAGTAGALVVKAAEAI
    VHDGVMATKGEMQIAGKGGGSPTVTAGAKATTSANKLSVDVASWDNAGSLDIKKGGAQVTVAGRYAEHGE
    VSIQGDYTVSADAIALAAQVTQRGGAANLTSRHDTRFSNKIRLMGPLQVNAGGPVSNTGNLKVREGVTVT
    AASFDNETGAEVMAKSATLTTSGAARNAGKMQVKEAATIVAASVSNPGTFTAGKDITVTSRGGFDNEGKM
    ESNKDIVIKTEQFSNGRVLDAKHDLTVTASGQADNRGSLKAGHDFTVQAQRIDNSGTMAAGHDATLKAPH
    LRNTGQVVAGHDIHIINSAKLENTGRVDARNDIALDVADFTNTGSLYAEHDATLTLAQGTQRDLVVDQDH
    ILPVAEGTLRVKAKSLTTEIETGNPGSLIAEVQENIDNKQAIVVGKDLTLSSAHGNVANEANALLWAAGE
    LTVKAQNITNKRAALIEAGGNARLTAAVALLNKLGRIRAGEDMHLDAPRIENTAKLSGEVQRKGVQDVGG
    GEHGRWSGIGYVNYWLRAGNGKKAGTIAAPWYGGDLTAEQSLIEVGKDLYLNAGARKDEHRHLLNEGVIQ
    AGGHGHIGGDVDNRSVVRTVSAMEYFKTPLPVSLTALDNRAGLSPATWNFQSTYELLDYLLDQNRYEYIW
    GLYPTYTEWSVNTLKNLDLGYQAKPAPTAPPMPKAPELDLRGHTLESAEGRKIFGEYKKLQGEYEKAKMA
    VQAVEAYGEATRRVHDQLGQRYGKALGGMDAETKEVDGIIQEFAADLRTVYAKQADQATIDAETDKVAQR
    YKSQIDAVRLQAIQPGRVTLAKALSAALGADWRALGHSQLMQRWKDFKAGKRGAEIAFYPKEQTVLAAGA
    GLTLSNGAIHNGENAAQNRGRPEGLKIGAHSATSVSGSFDALRDVGLEKRLDIDDALAAVLVNPHIFTRI
    GAAQTSLADGAAGPALARQARQAPETDGMVDARGLGSADALASLASLDAAQGLEVSGRRNAQVADAGLAG
    PSAVAAPAVGAADVGVEPVTGDQVDQPVVAVGLEQPVATVRVAPPAVALPRPLFETRIKFIDQSKFYGSR
    YFFEQIGYKPDRAARVAGDNYFDTTLVREQVRRALGGYESRLPVRGVALVAKLMDSAGTVGKALGLKVGV
    APTAQQLKQADRDFVWYVDTVIDGQKVLAPRLYLTEATRQGITDQYAGGGALIASGGDVTVNTDGHDVSS
    VNGLIQGRSVKVDAGKGKVVVADSKGAGGGIEADDEVDVSGRDIGIEGGKLRGKDVRLKADTVKVATSMR
    YDDKGRLAARGDGALDAQGGQLHIEAKRLETAGATLKGGKVKLDVDDVKLGGVYEAGSSYENKSSTPLGS
    LFAILSSTTETNQSAHANHYGTRIEAGTLEGKMQNLEIEGGSVDAAHTDLSVARDARFKAAADFAHAEHE
    KDVRQLSLGAKVGAGGYEAGFSLGSESGLEAHAGRGMTAGAEVKVGYRASHEQSSETEKSYRNANLNFGG
    GSVEAGNVLDIGGADINRNRYGGAAKGNAGTEEALRMRAKKVESTKYVSEQTSQSSGWSVEVASTASARS
    SLLTAATRLGDSVAQNVEDGREIRGELMAAQVAAEATQLVTADTAAVALSAGISADFDSSHSRSTSQNTQ
    YLGGNLSIEATEGDATLVGAKFGGGDQVSLKAAKSVNLMAAESTFESYSESHNFHASADANLGANAVQGA
    VGLGLTAGMGTSHQITNETGKTYAGTSVDAANVSIDAGKDLNLSGSRVRGKHVVLDVEGDINATSKQDER
    NYNSSGGGWDASAGVAIQNRTLVAPVGSAGFNFNTEHDNSRLTNDGAAGVVASDGLTGHVKGDANLTGAT
    IADLSGKGNLKVDGAVNAQNLKDYRDKDGGSGGLNVGISSTTLAPTVGVAFGRVAGEDYQAEQRATIDVG
    QTKDPARLQVGGGVKGTLNQDAAQATVVQRNKHWAGGGSEFSVAGKSLKKKNQVRPVETPTPDVVDGPPS
    RPTTPPASPQPIRATVEVSSPPPVSVATVEVVPRPKVETGSAASASAGGAQVVPVTPPKVEVAKVEVVPR
    PKVETAQPLPPRPVVAEKVTTPAVQPQLAKVETVQPVKPETTKPLPKPLPVAKVTKAPPPVVETAQPLPP
    VKPQKATPGPVAEVGKATVTTVQVQSAPPKPAPVAKQPAPAPKPKPKPKPKAERPKPGKTTPLSGRHVVQ
    QQVQVLQRQASDINNTKSLPGGKLPKPVTVKLTDENGKPQTYTINRREDLMKLNGKVLSTKTTLGLEQTF
    RLRVEDIGGKNYRVFYETNK
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : A combination of the 69-kDa outer membrane protein and filamentous hemagglutinin (fhaB), both isolated from lymphocytosis promoting factor (LPF; pertussis toxin) minus mutants of Bordetella pertussis, is protective in the mouse intracerebral challenge potency (Kendrick) test (Novotny et al., 1991).
  • Related Vaccine(s): B. pertussis FhaB and 69 kDa OMP protein vaccine
7. Prn
  • Gene Name : Prn
  • Sequence Strain (Species/Organism) : Bordetella pertussis Tohama I
  • VO ID : VO_0011033
  • NCBI Gene ID : 2664290
  • NCBI Protein GI : 33592195
  • Locus Tag : BP1054
  • Genbank Accession : BX640414
  • Protein Accession : NP_879839
  • Taxonomy ID : 257313
  • Gene Starting Position : 1098090
  • Gene Ending Position : 1100822
  • Gene Strand (Orientation) : +
  • Protein Name : pertactin precursor
  • Protein pI : 9.61
  • Protein Weight : 86606.91
  • Protein Length : 910
  • Protein Note : Identical to the previously sequenced Bordetella pertussis pertactin precursor Prn or Omp69A SW:PERT_BORPE (P14283) (910 aa) fasta scores: E(): 0, 100% id in 910 aa, and to Bordetella bronchiseptica pertactin precursor Prn SW:PERT_BORBR (Q03035) (911 aa) fasta scores: E(): 1.4e-160, 91.31% id in 921 aa
  • DNA Sequence : Show Sequence
    >gi|33591275:1098090-1100822 Bordetella pertussis Tohama I, complete genome
    AATGAACATGTCTCTGTCACGCATTGTCAAGGCGGCGCCCCTGCGCCGCACCACGCTGGCCATGGCGCTG
    GGCGCGCTGGGCGCCGCCCCGGCGGCGCATGCCGACTGGAACAACCAGTCCATCGTCAAGACCGGTGAGC
    GCCAGCATGGCATCCATATCCAGGGCTCCGACCCGGGCGGCGTACGGACCGCCAGCGGAACCACCATCAA
    GGTAAGCGGCCGTCAGGCCCAGGGCATCCTGCTAGAAAATCCCGCGGCCGAGCTGCAGTTCCGGAACGGC
    AGTGTCACGTCGTCGGGACAGTTGTCCGACGATGGCATCCGGCGCTTTCTGGGCACCGTCACCGTCAAGG
    CCGGCAAGCTGGTCGCCGATCACGCCACGCTGGCCAACGTTGGCGACACCTGGGACGACGACGGCATCGC
    GCTCTATGTGGCCGGCGAACAGGCCCAGGCCAGCATCGCCGACAGCACCCTGCAGGGCGCTGGCGGCGTG
    CAGATCGAGCGCGGCGCCAATGTCACGGTCCAACGCAGCGCCATCGTCGACGGGGGCTTGCATATCGGCG
    CCCTGCAGTCATTGCAGCCGGAAGACCTTCCGCCCAGCCGGGTGGTGCTGCGCGACACCAACGTGACCGC
    CGTGCCCGCCAGCGGCGCGCCCGCGGCGGTGTCTGTGTTGGGGGCCAGTGAGCTTACGCTCGACGGCGGG
    CACATCACCGGCGGGCGGGCAGCGGGGGTGGCGGCCATGCAAGGGGCGGTCGTGCATCTGCAGCGCGCGA
    CGATACGGCGCGGGGACGCGCCTGCCGGCGGTGCGGTTCCCGGCGGTGCGGTTCCCGGTGGTGCGGTTCC
    CGGCGGCTTCGGTCCCGGCGGCTTCGGTCCCGTCCTCGACGGCTGGTATGGCGTGGACGTATCGGGCTCC
    AGCGTGGAGCTCGCCCAGTCGATCGTCGAGGCGCCGGAGCTGGGCGCCGCAATCCGGGTGGGCCGCGGCG
    CCAGGGTGACGGTGTCGGGCGGCAGCTTGTCCGCACCGCACGGCAATGTCATCGAGACCGGCGGCGCGCG
    TCGCTTTGCGCCTCAAGCCGCGCCCCTGTCGATCACCTTGCAGGCCGGCGCGCATGCCCAGGGGAAAGCG
    CTGCTGTACCGGGTCCTGCCGGAGCCCGTGAAGCTGACGCTGACCGGGGGCGCCGATGCGCAGGGCGACA
    TCGTCGCGACGGAGCTGCCCTCCATTCCCGGCACGTCGATCGGGCCGCTCGACGTGGCGCTGGCCAGCCA
    GGCCCGATGGACGGGCGCTACCCGCGCGGTCGACTCGCTGTCCATCGACAACGCCACCTGGGTCATGACG
    GACAACTCGAACGTCGGTGCGCTACGGCTGGCCAGCGACGGCAGCGTCGATTTCCAGCAGCCGGCCGAAG
    CTGGGCGGTTCAAGGTCCTGACGGTCAATACGCTGGCGGGTTCGGGGCTGTTCCGCATGAATGTCTTCGC
    GGACCTGGGGCTGAGCGACAAGCTGGTCGTCATGCAGGACGCCAGCGGCCAGCACAGGCTGTGGGTCCGC
    AACAGCGGCAGCGAGCCGGCCAGCGCCAACACCCTGCTGCTGGTGCAGACGCCACTAGGCAGCGCGGCGA
    CCTTTACCCTTGCCAACAAGGACGGCAAGGTCGATATCGGTACCTATCGCTATCGATTGGCCGCCAACGG
    CAATGGGCAGTGGAGCCTGGTGGGCGCGAAGGCGCCGCCGGCGCCCAAGCCCGCGCCGCAGCCGGGTCCC
    CAGCCGCCGCAGCCGCCGCAGCCGCAGCCGGAAGCGCCGGCGCCGCAACCGCCGGCGGGCAGGGAGTTGT
    CCGCCGCCGCCAACGCGGCGGTCAACACGGGTGGGGTGGGCCTGGCCAGCACGCTCTGGTACGCCGAAAG
    CAATGCGTTGTCCAAGCGCCTGGGCGAGTTGCGCCTGAATCCGGACGCCGGCGGCGCCTGGGGCCGCGGC
    TTCGCGCAACGCCAGCAGCTGGACAACCGCGCCGGGCGGCGCTTCGACCAGAAGGTGGCCGGCTTCGAGC
    TGGGCGCCGACCACGCGGTGGCGGTGGCCGGCGGACGCTGGCACCTGGGCGGGCTGGCCGGCTATACGCG
    CGGCGACCGCGGCTTCACCGGCGACGGCGGCGGCCACACCGACAGCGTGCATGTCGGGGGCTATGCCACA
    TATATCGCCGACAGCGGTTTCTACCTGGACGCGACGCTGCGCGCCAGCCGCCTGGAGAATGACTTCAAGG
    TGGCGGGCAGCGACGGGTACGCGGTCAAGGGCAAGTACCGCACCCATGGGGTGGGCGCCTCGCTCGAGGC
    GGGCCGGCGCTTTACCCATGCCGACGGCTGGTTCCTCGAGCCGCAGGCCGAGCTGGCGGTATTCCGGGCC
    GGCGGCGGTGCGTACCGCGCGGCCAACGGCCTGCGGGTGCGCGACGAAGGCGGCAGCTCGGTGCTGGGTC
    GCCTGGGCCTGGAGGTCGGCAAGCGCATCGAACTGGCAGGCGGCAGGCAGGTGCAGCCATACATCAAGGC
    CAGCGTGCTGCAGGAGTTCGACGGCGCGGGTACGGTACACACCAACGGCATCGCGCACCGCACCGAACTG
    CGCGGCACGCGCGCCGAACTGGGCCTGGGCATGGCCGCCGCGCTGGGCCGCGGCCACAGCCTGTATGCCT
    CGTACGAGTACTCCAAGGGCCCGAAGCTGGCCATGCCGTGGACCTTCCACGCGGGCTACCGGTACAGCTG
    GTA
  • Protein Sequence : Show Sequence
    >gi|33592195|ref|NP_879839.1| pertactin precursor [Bordetella pertussis Tohama I]
    MNMSLSRIVKAAPLRRTTLAMALGALGAAPAAHADWNNQSIVKTGERQHGIHIQGSDPGGVRTASGTTIK
    VSGRQAQGILLENPAAELQFRNGSVTSSGQLSDDGIRRFLGTVTVKAGKLVADHATLANVGDTWDDDGIA
    LYVAGEQAQASIADSTLQGAGGVQIERGANVTVQRSAIVDGGLHIGALQSLQPEDLPPSRVVLRDTNVTA
    VPASGAPAAVSVLGASELTLDGGHITGGRAAGVAAMQGAVVHLQRATIRRGDAPAGGAVPGGAVPGGAVP
    GGFGPGGFGPVLDGWYGVDVSGSSVELAQSIVEAPELGAAIRVGRGARVTVSGGSLSAPHGNVIETGGAR
    RFAPQAAPLSITLQAGAHAQGKALLYRVLPEPVKLTLTGGADAQGDIVATELPSIPGTSIGPLDVALASQ
    ARWTGATRAVDSLSIDNATWVMTDNSNVGALRLASDGSVDFQQPAEAGRFKVLTVNTLAGSGLFRMNVFA
    DLGLSDKLVVMQDASGQHRLWVRNSGSEPASANTLLLVQTPLGSAATFTLANKDGKVDIGTYRYRLAANG
    NGQWSLVGAKAPPAPKPAPQPGPQPPQPPQPQPEAPAPQPPAGRELSAAANAAVNTGGVGLASTLWYAES
    NALSKRLGELRLNPDAGGAWGRGFAQRQQLDNRAGRRFDQKVAGFELGADHAVAVAGGRWHLGGLAGYTR
    GDRGFTGDGGGHTDSVHVGGYATYIADSGFYLDATLRASRLENDFKVAGSDGYAVKGKYRTHGVGASLEA
    GRRFTHADGWFLEPQAELAVFRAGGGAYRAANGLRVRDEGGSSVLGRLGLEVGKRIELAGGRQVQPYIKA
    SVLQEFDGAGTVHTNGIAHRTELRGTRAELGLGMAAALGRGHSLYASYEYSKGPKLAMPWTFHAGYRYSW
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Researchers constructed isogenic mutants of B. pertussis Tohama expressing the alleles ptxA1 or ptxA2 and prn1 or prn2 and compared the efficacies of an acellular pertussis vaccine against the mutants in a mouse model. While the vaccine was effective against all of the B. pertussis strains regardless of the allele expression pattern, the strain expressing ptxA1 and prn2 displayed a survival advantage over the other strains (Komatsu et al., 2010).
  • Related Vaccine(s): B. pertussis DNA vaccine encoding Prn
8. PtxA
  • Gene Name : PtxA
  • Sequence Strain (Species/Organism) : Bordetella pertussis Tohama I
  • VO ID : VO_0011034
  • NCBI Gene ID : 2665068
  • NCBI Protein GI : 33594638
  • Locus Tag : BP3783
  • Genbank Accession : BX640422
  • Protein Accession : NP_882282
  • Taxonomy ID : 257313
  • Gene Starting Position : 3988257
  • Gene Ending Position : 3989066
  • Gene Strand (Orientation) : +
  • Protein Name : toxin subunit 1
  • Protein pI : 7.54
  • Protein Weight : 27989.63
  • Protein Length : 269
  • Protein Note : Previously sequenced as Bordetella pertussis pertussis toxin subunit 1 precursor, NAD-dependent ADP-ribosyltransferase, PtxA SW:TOX1_BORPE (P04977) (269 aa) fasta scores: E(): 1.5e-110, 100% id in 269 aa
  • DNA Sequence : Show Sequence
    >gi|33591275:3988257-3989066 Bordetella pertussis Tohama I, complete genome
    GATGCGTTGCACTCGGGCAATTCGCCAAACCGCAAGAACAGGCTGGCTGACGTGGCTGGCGATTCTTGCC
    GTCACGGCGCCCGTGACTTCGCCGGCATGGGCCGACGATCCTCCCGCCACCGTATACCGCTATGACTCCC
    GCCCGCCGGAGGACGTTTTCCAGAACGGATTCACGGCGTGGGGAAACAACGACAATGTGCTCGACCATCT
    GACCGGACGTTCCTGCCAGGTCGGCAGCAGCAACAGCGCTTTCGTCTCCACCAGCAGCAGCCGGCGCTAT
    ACCGAGGTCTATCTCGAACATCGCATGCAGGAAGCGGTCGAGGCCGAACGCGCCGGCAGGGGCACCGGCC
    ACTTCATCGGCTACATCTACGAAGTCCGCGCCGACAACAATTTCTACGGCGCCGCCAGCTCGTACTTCGA
    ATACGTCGACACTTATGGCGACAATGCCGGCCGTATCCTCGCCGGCGCGCTGGCCACCTACCAGAGCGAA
    TATCTGGCACACCGGCGCATTCCGCCCGAAAACATCCGCAGGGTAACGCGGGTCTATCACAACGGCATCA
    CCGGCGAGACCACGACCACGGAGTATTCCAACGCTCGCTACGTCAGCCAGCAGACTCGCGCCAATCCCAA
    CCCCTACACATCGCGAAGGTCCGTAGCGTCGATCGTCGGCACATTGGTGCGCATGGCGCCGGTGATAGGC
    GCTTGCATGGCGCGGCAGGCCGAAAGCTCCGAGGCCATGGCAGCCTGGTCCGAACGCGCCGGCGAGGCGA
    TGGTTCTCGTGTACTACGAAAGCATCGCGTATTCGTTCTA
  • Protein Sequence : Show Sequence
    >gi|33594638|ref|NP_882282.1| toxin subunit 1 [Bordetella pertussis Tohama I]
    MRCTRAIRQTARTGWLTWLAILAVTAPVTSPAWADDPPATVYRYDSRPPEDVFQNGFTAWGNNDNVLDHL
    TGRSCQVGSSNSAFVSTSSSRRYTEVYLEHRMQEAVEAERAGRGTGHFIGYIYEVRADNNFYGAASSYFE
    YVDTYGDNAGRILAGALATYQSEYLAHRRIPPENIRRVTRVYHNGITGETTTTEYSNARYVSQQTRANPN
    PYTSRRSVASIVGTLVRMAPVIGACMARQAESSEAMAAWSERAGEAMVLVYYESIAYSF
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : BALB/c mice were immunized with PTx vaccine on day 6 of life and then challenged with B. pertussis using the aerosol challenge model. These primed mice were significantly better protected against leukocytosis, weight loss, and proliferation of B. pertussis in the lungs following aerosol challenge than the nonprimed group. This protection correlated with levels of anti-PT antibody in serum present on the day of aerosol challenge (Bruss and Siber, 2002).
  • Related Vaccine(s): B. pertussis PTx protein vaccine
9. PtxB
  • Gene Name : PtxB
  • Sequence Strain (Species/Organism) : Bordetella pertussis
  • VO ID : VO_0011037
  • NCBI Protein GI : 225311180
  • Other Database IDs : CDD:112265
    CDD:145854
    GOA:C0MPK7
    UniProtKB/TrEMBL: C0MPK7
  • Taxonomy ID : 520
  • Gene Strand (Orientation) : ?
  • Protein Name : pertussis toxin subunit 2 precursor
  • Protein pI : 8.44
  • Protein Weight : 23409.78
  • Protein Length : 226
  • Protein Note : Aerolysin/Pertussis toxin (APT) domain; pfam03440
  • Protein Sequence : Show Sequence
    >gi|225311180|emb|CAX52304.1| pertussis toxin subunit 2 precursor [Bordetella pertussis]
    MPIDRKTLCHLLSVLPLALLGSHVARASTPGIVIPPQEQITQHGGPYGRCANKTRALTVAELRGSGDLQE
    YLRHVTRGWSIFALYDGTYLGGEYGGVIKDGTPGGAFDLKTTFCIMTTRNTGQPATDHYYSNVTATRLLS
    STNSRLCAVFVRSGQPVIGACTSPYDGKYWSMYSRLRKMLYLIYVAGISVRVHVSKEEQYYDYEDATFET
    YALTGISICNPGSSLC
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : BALB/c mice were immunized with PTx vaccine on day 6 of life and then challenged with B. pertussis using the aerosol challenge model. These primed mice were significantly better protected against leukocytosis, weight loss, and proliferation of B. pertussis in the lungs following aerosol challenge than the nonprimed group. This protection correlated with levels of anti-PT antibody in serum present on the day of aerosol challenge (Bruss and Siber, 2002).
  • Related Vaccine(s): B. pertussis PTx protein vaccine
10. PtxC
  • Gene Name : PtxC
  • Sequence Strain (Species/Organism) : Bordetella pertussis
  • VO ID : VO_0011038
  • NCBI Protein GI : 225311183
  • Other Database IDs : CDD:112265
    CDD:145854
    GOA:Q546I1
    InterPro: IPR005138
    UniProtKB/TrEMBL: Q546I1
  • Taxonomy ID : 520
  • Gene Strand (Orientation) : ?
  • Protein Name : pertussis toxin subunit 3 precursor
  • Protein pI : 8.87
  • Protein Weight : 23895.72
  • Protein Length : 227
  • Protein Note : Aerolysin/Pertussis toxin (APT) domain; pfam03440
  • Protein Sequence : Show Sequence
    >gi|225311183|emb|CAX52307.1| pertussis toxin subunit 3 precursor [Bordetella pertussis]
    MLINNKKLLHHILPILVLALLGMRTAQAVAPGIVIPPKALFTQQGGAYGRCPNGTRALTVAELRGNAELQ
    TYLRQITPGWSIYGLYDGTYLGQAYGGIIKDAPPGAGFIYRETFCITTIYKTGQPAADHYYSKVTATRLL
    ASTNSRLCAVFVRDGQSVIGACASPYEGRYRDMYDALRRLLYMIYMSGLAVRVHVSKEEQYYDYEDATFQ
    TYALTGISLCNPAASIC
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : BALB/c mice were immunized with PTx vaccine on day 6 of life and then challenged with B. pertussis using the aerosol challenge model. These primed mice were significantly better protected against leukocytosis, weight loss, and proliferation of B. pertussis in the lungs following aerosol challenge than the nonprimed group. This protection correlated with levels of anti-PT antibody in serum present on the day of aerosol challenge (Bruss and Siber, 2002).
  • Related Vaccine(s): B. pertussis PTx protein vaccine
11. PtxD
  • Gene Name : PtxD
  • Sequence Strain (Species/Organism) : Bordetella pertussis
  • VO ID : VO_0011032
  • NCBI Protein GI : 225311181
  • Other Database IDs : CDD:90471
    GOA:C0MPK8
    UniProtKB/TrEMBL: C0MPK8
  • Taxonomy ID : 520
  • Gene Strand (Orientation) : ?
  • Protein Name : pertussis toxin subunit 4 precursor
  • Protein pI : 10.99
  • Protein Weight : 15253.97
  • Protein Length : 152
  • Protein Note : Pertussis toxin S4 subunit; pfam09275
  • Protein Sequence : Show Sequence
    >gi|225311181|emb|CAX52305.1| pertussis toxin subunit 4 precursor [Bordetella pertussis]
    MLRRFPTRTTAPGQGGARRSRVRALAWLLASGAMTHLSPALADVPYVLVKTNMVVTSVAMKPYEVTPTRM
    LVCGIAAKLGAAASSPDAHVPFCFGKDLKRPGSSPMEVMLRAVFMQQRPLRMFLGPKQLTFEGKPALELI
    RMVECSGKQDCP
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : BALB/c mice were immunized with PTx vaccine on day 6 of life and then challenged with B. pertussis using the aerosol challenge model. These primed mice were significantly better protected against leukocytosis, weight loss, and proliferation of B. pertussis in the lungs following aerosol challenge than the nonprimed group. This protection correlated with levels of anti-PT antibody in serum present on the day of aerosol challenge (Bruss and Siber, 2002).
  • Related Vaccine(s): B. pertussis PTx protein vaccine
12. PtxE
  • Gene Name : PtxE
  • Sequence Strain (Species/Organism) : Bordetella pertussis
  • VO ID : VO_0011039
  • NCBI Protein GI : 225311182
  • Other Database IDs : CDD:117820
    GOA:C0MPK9
    UniProtKB/TrEMBL: C0MPK9
  • Taxonomy ID : 520
  • Gene Strand (Orientation) : ?
  • Protein Name : pertussis toxin subunit 5 precursor
  • Protein pI : 6.5
  • Protein Weight : 14003.11
  • Protein Length : 133
  • Protein Note : Pertussis toxin S5 subunit; pfam09276
  • Protein Sequence : Show Sequence
    >gi|225311182|emb|CAX52306.1| pertussis toxin subunit 5 precursor [Bordetella pertussis]
    MQRQAGLPLKANPMHTIASILLSVLGIYSPADVAGLPTHLYKNFTVQELALKLKGKNQEFCLTAFMSGRS
    LVRACLSDAGHEHDTWFDTMLGFAISAYALKSRIALTVEDSPYPGTPGDLLELQICPLNGYCE
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : BALB/c mice were immunized with PTx vaccine on day 6 of life and then challenged with B. pertussis using the aerosol challenge model. These primed mice were significantly better protected against leukocytosis, weight loss, and proliferation of B. pertussis in the lungs following aerosol challenge than the nonprimed group. This protection correlated with levels of anti-PT antibody in serum present on the day of aerosol challenge (Bruss and Siber, 2002).
  • Related Vaccine(s): B. pertussis PTx protein vaccine
13. S1
  • Gene Name : S1
  • Sequence Strain (Species/Organism) : Bordetella pertussis Tohama
  • NCBI Protein GI : 3152313
  • Other Database IDs : CDD:111768
    GOA:Q599G4
    HSSP: P04977
    InterPro: IPR003898
    UniProtKB/TrEMBL: Q599G4
  • Taxonomy ID : 520
  • Gene Strand (Orientation) : ?
  • Protein Name : toxin subunit S1
  • Protein Length : 269
  • Protein Note : Pertussis toxin, subunit 1; pfam02917
  • Protein Sequence : Show Sequence
    >gi|3152313|emb|CAA06899.1| toxin subunit S1 [Bordetella pertussis]
    MRCTRAIRQTARTGWLTWLAILAVTAPVTSPAWADDPPATVYRYDSRPPEDVFQNGFTAWGNNDNVLDHL
    TGRSCQVGSSNSAFVSTSSSRRYTEVYLEHRMQEAVEAERAGRGTGHFIGYIYEVRADNNFYGAASSYFE
    YVDTYGDNAGRILAGALATYQSEYLAHRRIPPENIRRVTRVYHNGITGETTTTEYSNARYVSQQTRANPN
    PYTSRRSVASIVGTLVRMAPVIGACMARQAESSEAMAAWSERAGEAMVLVYYESIAYSF
  • Molecule Role : Protective antigen
  • Related Vaccine(s): B. pertussis DNA vaccine pcDNA/S1
14. TcfA
  • Gene Name : TcfA
  • Sequence Strain (Species/Organism) : Bordetella pertussis
  • NCBI Protein GI : 282766137
  • Other Database IDs : CDD:154874
  • Taxonomy ID : 520
  • Gene Strand (Orientation) : ?
  • Protein Name : tracheal colonization factor
  • Protein pI : 5.91
  • Protein Weight : 62423.78
  • Protein Length : 631
  • Protein Note : Autotransporter beta-domain; cl02365
  • Protein Sequence : Show Sequence
    >gi|282766137|gb|ADA85103.1| tracheal colonization factor [Bordetella pertussis]
    MHIYGNMNRATPCRGAVRALALALLGAGMWTLSPPSAWALKLPSLLTDDELKLVLPTGMSLEDFKRSLQE
    SAPSALATPPSSSPPVAKPGPGSVAEAPSGSGHKDNPSPPVVGVGPGMAESSGGHNPGVGGGTHENGLPG
    IGKVGGSAPGPDTSTGSGPDAGMASGAGSTSPGASGGAGKDAMPPSEGERPDSGMSDSGRGGESSAGGLN
    PDGAGKPPREEGEPGSKSPADGGQDGPPPPRDGGDADPQPPRDDGNGEQQPPKGGGDEGQRPPPAAGNGG
    NGGNGNAQLPERGDDAGPKPPEGEGGDEGPQPPQGGGEQDAPEVPPVAPAPPAGNGVYDPGTHTLTTPAS
    AAVSLASSSHGVWQAEMNALSKRMGELRLTPVAGGVWGRAFGRRQDVDNRVSREFRQTISGFELGADTAL
    PVADGRWHVGAVAGYTNGRIKFDRGGTGDDDSVHVGAYATYIEDGGFYMDGIVRVSRIRHAFKVDDAKGR
    RVRGQYRGNGVGASLELGKRFTWPGAWYVEPQLEVAAFHAQGADYTASNGLRIKDDGTNSMLGRLGLHVG
    RQFDLGDGRVVQPYMKLSWVQEFDGKGTVRTNDIRHKVRLDGGRTELAVGVASQLGKHGSLFGSYEYAKG
    S
  • Molecule Role : Other
  • Molecule Role Annotation : Intranasal administration of IEM101 expressing Tcf induced a significant reduction in bacterial colonization of the tracheas of mice challenged with wild-type B. pertussis. These data are in agreement with the putative role of Tcf in Bordetella tracheal colonization (Chen et al., 1998).
  • Related Vaccine(s): VC-TetC/Tcf
1. IgG
  • Gene Name : IgG
  • Sequence Strain (Species/Organism) : Mus musculus
  • NCBI Gene ID : 16059
  • Genbank Accession : AF010213
  • Taxonomy ID : 10090
  • Chromosome No : 12
  • Gene Starting Position : 881411
  • Gene Ending Position : 914690
  • Gene Strand (Orientation) : +
  • Protein Name : immunoglobulin heavy chain (V7183 family)
  • Protein Note : Also known as IgG; IgH; VI24H; VH7183; B9-scFv; IgVH1(VSG)
  • DNA Sequence : Show Sequence
    >gi|94393741:881411-914690 Mus musculus strain 129/SvJ chromosome 12 unlocalized genomic contig, MGSCv37 alternate locus group 129/SvJ
    CATGGACTTTGGGCTCAGCTGTGTTTTCCTTGTCCTCATTTTAAGAGGTAATTTGTAGAAATAAGATCCT
    GCCAGTATTGTGTACAGGAGAAATAGAAAAATTTTTCTTTCCTCTATTTTGTTTTGTTTTGTTAGTGACA
    GTTTACAAATAAGCATTCTCTGTTGTGAGGTGCCCAGTGTGAGGTGAAGATGGTGGAGTCTGTGGGAGGC
    TTAGTGCAGCCTGTAGGGTCATTGAAACCCTCCTGTGCAGCCTCTGGATTCATTCTCACTGACTACTGAA
    TGACCTGGATCCTTCAGGCTTCAAAGAAAAGGATGGAGAGGGTGACAATAAAATTTTTCCCACTCACACC
    CACTTGCTGGCCCTGGCGTTCCCCTGTAATGAGGCACATAAAGTTTGCAAAACCAAGGGGCCTCTCTTCT
    CAATGATGGCTGACTAGGACATCTTCTGATACATATGCAGCTAGAGACATGAGCTCCCGGGATACTGGTT
    ACTTCATATTGTTGTTCCCCCACAACAGTTGCAGACCCTTTTATTTCTGTGGGTACTTTCACTAGCTCCT
    CCATTGGGGGCCCTGTGTTCCATCCAATAGCTGACTGTGAGCATCCACTTCTGTAGTTGCTAGGCCCCGG
    CATAGCCTCACAAGAGACAGCTATATCAGGGTCCTTTCAGCAAAATCTTGCTGGTGTATGCAATGGTGTC
    AGAGTTTGGAGTCTGATTATGGGATGGATCCCCAGGTATGGCAAACTCTAGATGGTCCATCCTTTCCCAA
    CAATAATTTTTAATGGTGGAGATAGCACCTACTATCCAGACACAATGAAGGGCCAATTCACTATCTCTAG
    AGATGATGCCAAAAACACACTTTACCTGAAAATAAACAGTCTGAGGTCTGAGTACACAGCCATGTATACA
    TATATTCCTAAGCTTGAGTAAGTGGACTTAAACTGATTCCATCACAACTTGCATGAGATGGATATTCCCC
    AGTGTTAAGACCTGTCACCATCACTGTCAATCAGAAGACAAAGTTTATGCACAACAAAACAAAAAAACCA
    AAAGCAGAGGCCTCCAATTACAAGTAATAGACCCAGACCCACAGTCTCTGAAAACTGACTGTACAGTTGG
    ATCCAGTCTTTTACTTCTTTTCCCTGGATTTTATATTACTGAGGAAATGAGGAAAGCTCTACAATATCTG
    TTCTCCATAGTGCTCAACACCTCCAAGCACAGGTTACCCATATTCATGCCTGCCTTCTGCTACACTTCTT
    GTCTTGTAGACTACTTCAACCTATTTTGTACTCCAGTTAATGAAACTCAAGTCTAGCAGCCTGTCACTGT
    TTATTCTAAAGTATTATGAACAGGTGACCTCCCATCCTTCCCCAACGCAATAATCATATTTAGGAATTTG
    AGGTTTTATGAGATATGATCTCAGGGTAGAGAGAGAAAGCAAACTACATAGAAATATAGACTGACATAAA
    TCAAGACTTGCATAAGCTAGTCCCCAAGTTCCATGTCCCTAAGTGGCAAGGACTATCTTCTGAGCCTAAT
    GAGATGAGATCCAAATCAAACCTCCTGGGTCTTTTTAGATAAACATGTGAGATCAATAGACTAAATGCTT
    TGGCTGGGCTTCCTTGCAATCCAATTCCCAAACAAAAATGGATCTGGCTCCACAGACACCACAAGAATAG
    TCTTAAATAGTTCTTTAAGTAGAATGTCTGATCACTACGAGCCCAATTCCATCCTAAATACTCTTCTGGA
    TTATACATAAATAAAAATTGAACATAGGGCATGGGGCACTGATCTCCCTGTGCTACATGAATGGGGGCTC
    ATTTACTAAATGTTCCCATTTTTCTTTCTAGCGCTGCACAGTGCAAATCCTACAACTTCCTGTTTATCTA
    CAATGTGAACTCCAAACAGTACAAGAAAAAACGTTCCTTATGTTCCTCTCCAGGTTCTCCAACAAGCACA
    GAGCAACCTTCTGTCACCAGGACGGAAAACTGGAAACCTTGCTCACTGCTTCCTTTTATTCCCTCGGGAA
    CCTCCCCCAATGCAAAGCAGCCCTCAGGCAGAGGATAAAAGCTCACACAAAGACGAGAAGCCCCATCCTC
    TTCTCATAGAGCATCCATCAGAGCATGGCTGTCCTGGGGCTGCTTCTCTGCCTGGTGACTTTCCCAAGCT
    GTAAGTGTTTCAGGGTTTCAGAAGAGGGACTAAGACATGTCAGCTAGAAGATGTGTGACTAATGGTGATG
    TTGCTTGTCCCCAGGTGTCCTGTCCCAGGTGCAGCTGAAGGAGTCAGGACCTGGCCTGGTGGCGCCCTCA
    CAGAGCCTGTCCATCACATGCACCGTCTCAGGGTTCTCATTAACTAGCTATGGTGTACACTGGGTTCGCC
    AGCCTCCAGGAAAGGGTCTGGAGTGGCTGGTAGTGATATGGAGTGATGGAAGCACAACCTATAATTCAGC
    TCTCAAATCCAGACTGAGCATCAGCAAGGACAACTCCAAGAGCCAAGTTTTCTTAAAAATGAACAGTCTC
    CAAACTGATGACACAGCCATGTACTACTGTGCCAGAAACACAGTGTGGGAAGTCCAATGTGAGCCTGCAC
    AAATACTTCTCTGCAGGGATGATCACAACCAGCAGGGGGCGCTGATGACCCAAAGGGACTTCCCAGGATC
    TCTTCTGGAATCTAGGGAGTTCTGGCCTGTGTCTATCAGCATGTGTTTCAATGTTAGAGTTGTGAGTTTT
    CCTTCCAGCAACAGAGATATTTTAGAGCCCACTTTTCATGGTCATTCTACTAAATTTGTTCACATAGTGG
    AAAGATTTGTTAAATGATTCTATAGTCTAATAGGGTCAAACAAAAACAAATAATTGAGTTCATATCTACC
    AAAAAAAAAAAAATTCCCTCAAAGTGGACAACTGTGTAGGTGAGGAAAACCAGGGGGATTTGGGAATAGA
    TTATTTCTCTCCCGACTGTGGTGTTAGTCACCTTTCAGCCATTTACTGTATTTAATTCATGTTTAAAGTT
    AATTGTATTCATCTTCCCTAACATGAAGTTTTCAAACACATGTCCACAATTTAATGATGACACAGTTATC
    ATTGTGAATGATAACTCATAAGATCTCTCTCCATATATGAAACACACGATATTCTGTTATTAGCTATAGC
    CAACAAAGTTACATATCATTATTATTACTGAAATAATTCTTCCCATCTAACTGAATAGTTTTCTCACTCG
    ACACTGCCTATGCTGCGATCAGCCTGCTCTAATTTTACCTTTGCTCAGAGCACTGCTTTCTGTTTCATTT
    GATAAGATGGTGCCTGGTTGTCACTGAAAATGTGTCCTCCAGTTTCACAGTGATTAATGTGATTTTCAGT
    ACATTGAGAACAGAGCCACAGCAAAAATGAGATGGAATGTCATCATTTTTACGCCAGGTGCTGCAGAAAT
    AGCTAGGTGGTTAAGAGAGAATATTGAACTTTGAGGGGTTCAGATTAAATTCCTGATACCCACAATGTGC
    ACCTCATAACCACATGTACATATAGAAAACTCAGTATAAATGTGGCCTCCGTGAGCACCACACTACTCCC
    ACAAACACATATACACATAATTAAAAGTAAAGATTTTAGAAAAATGGCTAATCTAATGATAGGAAGTAGT
    CAAAAAGAGAGTTCTTTTGTCATGTACATATGTGTAGCAGACTTAAATGTTAAACATTCAAGAATACATT
    CCTCGATCCACATTAAAATTTTGCAAAGAGTAGCACAGACGGTGGCAATTGCTAAACTTATATCTAGAAA
    CACAATTATGTGTGGTGATATTTAATTACACATTTATACCAGGACATATGACAATATGGAAACCAAACAT
    GTTGTATCCACATGCTCTAAGGAAAACTAAATGGAGTGTGATAAAACCAAAGAAAATGTGAATATGAAAT
    ATTTTTCCAACTCTGCATCTTAAAACGGTTTCTTTCATGTGTCATATCTGCTATGAGGACTTTCTTCTGC
    CCATGTCCAACTCCAGAGCATGCCACAGCAGGAAGACCTACAGGTATTACTTCTCTGCACCCAGGAAAAC
    CACCTCTGTCCTGACCCTGCAGCTCTCAGAAGAGCCCAGACCTTCATTCTCAGGCCCTCATCCAGTAATC
    AGCACTGAATACAGAGCACTCACCATGGACTTTGGGCTCAGCTTGGTTTTCCTTGTCCTTATTTTAAAAG
    GTAATTCATAGAGATAAGATTCTATCTGTTTTGTGTACATGAGAAACAGAAAAATTGTATTGTTTCTCTA
    TTTTGTTTTGTTTTGTTAGTGACAGTTTCTGACTCAAGATTCTCTGTTTGAAGGTACCCAGTGTGAGGTG
    AAGCTGGTGAAGTCTAAGGGGAGGCATAGTGCAGCCTAGAAGGTCCATGATACTCTACTGTGCAGCCTCG
    GATTCACTGTAAGTGACGACTGGTTTGTCCGTGTTTGCCAGGCTCCAAAGAAGGGGCTGCAGTGGGGGAT
    GGGAATAATTTTTCATGGTTGTGGTAGCCCCTCTTATGCAGACACCTTGAAGAAGTGGGTTGGACGTAAC
    ATATTCAGAATCAATATTTAAAGATTCTAATCCTTGAAGATATCACTTTTGACCAAGTATATATGAACCA
    TGTTACTGAGGTTTATGGAGGTTTGAGTATGTTAGGTCCATGGATAGGGAAAATATTAGGGGATTTTAGG
    AGTAACTGAGGCTTGTTGTAGGAAGGACATCACTGTAGGGGTAGGCTCCGTGTTCCTATCTTCAAGCTCT
    ACCCAGTGCAGAATAGAGCCCTCTTCTGCCGGCAAGTGGAAAGAGTTTCTCTTCCTGGCTGCCTTCAATC
    CAAGTTGTAGAATATCAAATCTCCTAACACTATGACTGCGAGCATGCTGACATGCGTCCCACCATAAAAA
    TAGACTGAACCTCTGAAGCTTTAAGCCAGCCTCTAGTAACTGTATTCTTTAATAAGACTGAACTTGGCTA
    TGGTGTCTTTTCACAGTAAAATGGAAACATAGACAAGGTTCTAACTCTCTGTACTAGAGGACCATCTCTA
    TGTCCTTGGTGTTGTATGTAAATTATTGAACAAATACTATAGACAAGTTGTATGGCCAAAAGTCCATCCC
    CTTCAACAATCTACTATCTGGAACCATATAGATTAGATTCCTTTCCTGCACTCATTTCCCTTACTTGCTG
    AGACATTTTGAAGACATGCTCAGAATCCCTGAACTTCCTGCTGAAAAAAAAATACCCCTCCAATTTGAAG
    ACAGTTCTCTTCCAAAATTCATCATAAATACTGATCCACATGTCCAGGCATATCATGTAGTTTTAAAAAA
    CAAACCAATCAATGCTAAAGTGGGTAAGTGCCTACATCATTGGTTTATGTCTGTTCATAACCTGGTATAT
    AGCTAGAGACCAGGACTGCATGTTTCTCCTAGGCCACACCTCTCCCACAAATGCTGGCTCTGCCTCTCCA
    GAATTCCAAGATCATGGATCTCTGGGTCCCCAAGGAACAATAAGTGTGCACTCTTGCCAGCCTGTACACT
    ACTGCACTAGCTTCTCCCCCTGGAGCTTGGTCATTGCTCAATCTTCCCTTTCCAAAGCCTGGCCAAATTC
    CTCCTACCTTTTGTTCTTTCAGTCAGGCCACCTAAGTCATCTTGAATGAAAAACAACACAAAATCTGAAC
    TTAAAATCAACAAATAATACAAGTGCTGCGCACAAAATCAATCATTCTAAACTCATCAACTATTTTATGA
    TGGAAATCTTCCAACATACAAGCTACCACCAGGTCTAAGAATTACTCATCTACATGTTGCTTCCTCTCAC
    TCACAGCCTAACCATAAAAGGGCTGTTTCTTCCTCCCATGTCCCCTCTTTTGCCTTCAGAAGCAGAAGCT
    CCACCTCCTCCTCTTTGCCCAGCAATTGGCTTCTTGTCGTCTTTATTATCATATTAATTACTTAGGGGAA
    AATCCCGTGTAGTGGCTATTCCTGGTTGTCAACTTGACAATATTTGGAATGAACTACAATCCGGAATTGG
    AAGGCTCACCAGTGACCCTTATCTGGAGGCTTGGAGATCCTTATCTGGATCTTGGTTTGAAGATCTTGAG
    CCATAGGGGCTATGGATTCCAGAAGATTGAATCTCCGAGTTTAAGGAACACACCTTTAATCTGGGCTACG
    CCTTTCATCTGGGATTAAAGGTGTGGCGGAACACACCTTTAATCTGGACTACACCTTCTGCTGGAGACAA
    TATAAGGACATTGAAAGAAGGGAGTCTAGCTCTTGCTCTTGCTCCTTCGCCTGCTTGCTGCGTGAGACTG
    AGTAACTGCTAGATCCTTGGACTTCCATTCACAGCTGCGACTGAACAATTGTTGGGAATTGGGCTGCCGA
    CTCTAAGTCATCAATAAATTCCTTTACTATCTAGAGACTATCCATAGTTCTGTGACTCTAGAGAACCCTG
    ACTAATACAGAAGTTGGTACCAGGAGTGGTTCTAGAGTAACAGAAGTACAAGGATGAATCTTTTAAAATA
    CTGGAATTGGCTTGTTGATCCACCAGCACTTTCAACTATTGAAACCTCTCCAGATTCTCTCCCTCCTGGG
    AGCTCAGAGAATTTTGAAGACCCATGGTTGAAACTATATTCCGAACTTAAAGAAGCAAATGCCCTTGATT
    TTCTTAATGAATTAGGTGATTCAGTGCACAAAGCTTTCTACAAGATGGGGAAAAAATTGGAAAATGATTT
    TACTGGCTGGCTGCTCTTAGTATCTGTGGAAAAAATGATGAATGAAAGGAAGGAGTTGTGTGATAAAATC
    GAAAGGCTCCAGACACAAGTAAACGATCTAAAAGTTGCTAAGTGTGTCCTTGAGGAGAATCTTCTCTCTT
    GTAGCAATAGAGCTCAAGTTGCAGAAAATCAAACAGAAACTCTCATTGTAAGGTTGGCTGAACTACAGCG
    AAAATTCAAGTCTCAGCCTCAGAGTGTGTCAACAGTTAAAGTAAGGGCTCTAATTGGCAAAGAATGGGAT
    CCTACAACATGGGACGGGGATGTGTGGGAAGACCATGTTGAAGCTGAGAATTTTGAATCTTCAGATTCTC
    AAGGGTTTGCCCCACCTGAGGAAGTAGTACCCTCAGCCCCACCCCTTGAAATAATGCCTTCCCCACATGA
    GGAAATTAATTTTGCAGAGTCTGATAAACCAGCAATGATTTTCACTACTGATGTTTCTCAAGGCCCACCA
    ATAGTTTCTTCTAGACCTGTAACCAGACTCAAAGCAAAACAGGCTCCTAGAGGGGAGGTAGAAAGTGTAG
    TCCATGAGGAAATTCGCTACACTACTAAGGAGCTTAATGAGTTTGCTAATTCATTCAAGCAGAAACCTGG
    TGAATATGTGTGGGAATGGATTTTAAGGGTGTGGGATAAGGGTGGAAGGAACATAAGACTAGAGCAGGCT
    GAGTTTATTGACATGGGTCCTCTGAGTAGAGATTCTAGGTTTAATACGGAAGCTCGCATAATTAAAAAAG
    GTGTCAAAAGTTTGTTTGAATGGTTGGCTGAGGTGTTTATCAAAAGATGGCCTACTGGAAATGACTTGGA
    GATGCCTGATATTCCGTGGCTTAGTGTTGATGAAGGGATTTTAAGACTTAGGGAAATTGCAATGCTAGAG
    TGGATATATTGTGTAAAGCATAATTGTCCACAATGGGAAGGTCCAGAAGATATGCCTTTCACTAGCTCTA
    TAAGACGCAAATTGGTGAGAGGGGCACCAGCACATTTGAAGGGTTTTGTTCTTTCCCTTTTCCTTGTACC
    AGATCTTAGCATTGGAGATGCTTCTGCTCAATTAGATGAATTAAATTCACTGGGTTTAGTTGGATTCCGA
    GGTAACAAGGGCCAGGTGGCAGCATTGAATCGCCGGAGACAAGGTGATTCTAGTTATTATAATGGACAGC
    GTAGACAAAAGAATGTTTATAATAACATACCCAGCAATGGTCAGCACAGGAGAGGTGAAATTTATAATGG
    CATGACTCGGTTGGACCTTTGGTACTGGCTAACCAATCATGGTGTTTCCAGGAATGAAATACATAGGAAG
    CCTACTGCATATTTGTTTGATCTGTATAAGCAGAAAAATTCTCAAACAAATGAAAGAAAGGCTACATTAG
    ATCATGGTAAACAGCAATCTCGGCCAGTGAATCAATTTCCAGACTTGAGACAGTTTGCAGATCCAGAACC
    CCTTGAATGAAGGGGTGGCCAGGTTCCGCTGAGGAAGGATCTTGATAAGACACCCAAAGGTTTTGCTGTT
    ACCCTTTCTCCAGTTCTTCCCCAGAGGGACCTAAGGCCTTTTACAAGGGTAACTGTACACTGGGGAAAAG
    GAAATAATCAGACTTTTCAGGGTCTGCTGGATACTGGTTCTGAGTTGACACTGATTCCAGGGGATCCCAA
    GAAACATTGTGGCCCTCCAGTTAAAGTAGAGGCTTATGGAGGGCAGGTGATTAATGGAGTTTTGACTGAT
    GTCCGACTCACAATAGGTCCAGTAGGTCCCCAGACACATCCTGTGGTGATTTCCCCAGTTCCAGAATGTA
    TAATTGGGATAGATATACTCAGAAATTGGCAGAATTCTCATATTGGTTCCCTGAACTGTAGAGTGAGGGC
    TATTATGGTTGGAAAGGCCAAATGGAAACCTTTAGAGTTGCCTCTGCCAAAGAAAATAGTGAATCAAAAA
    CAGTATCGTATTCCTGGAGGCATTGCAGAAATTACTGCCACTATCAAGGACTTGAAAGATGCAGGGGTGG
    TGGTTCCCACCACATCTCCGTTTAACTCTCCTATCTGGCCAGTGCAGAAAACAGATGGATCATGGAGAAT
    GACAGTTGATTATCGAAAACTAAATCAGGTAGTAACTCCAATTGCAGCTGCTGTACCAGATGTAGTTTCA
    TTACTTGAGCAAATTAACACATCTCCTGGCACCTGGTATGCGGCTATTGATCTGGCAAATGCCTTCTTCT
    CAGTACCTGTCCATAAGGACCACCAGAAGCAATTTGCTTTCAGTTGGCAAGGCCAACAGTATACTTTCAC
    AGTTTTGCCTCAAGGATATATTAACTCTCCTGCCCTGTGTCATAATTTAGTTAGAAGGGATCTTGATCGT
    TTGGATCTTCCACAAAATATCACATTGGTGCACTATATTGATGACATTATGCTGATTGGACCAAGTGAGC
    AGGAAGTAGCAACCACTTTGGACTCATTGGTAACACATATGCGTATCAGAGGATGGGAAATAAATCCAAC
    CAAAATTCAAGGACCATCTACCTCAGTGAAATTCTTAGGAGTCCAGTGGTGTGGAGCATGCAGAGATATT
    CCTTCTAAGGTGAAAGATAAGTTATTGCACCTGGCCCCTCCTACAACCAAGAAAGAAGCACAACGTTTAG
    TGGGTCTATTTGGATTCTGGAGACAACACATCCCTCACTTGGGTGTGTTACTTAGGCCTATTTACCAAGT
    GACTCGGAAAGCTGCTAGCTTTGTGTGGGGCCTGGAACAGGAGAAGGCCCTTCAACAGGTCCAGGCTGCT
    GTGCAGGCTGCACTACCACTTGGACCATATGACCCAGCAGACCCGATGGTACTTGAGGTGTCTGTGGCTG
    ATAGAGATGCTGTTTGGAGCCTCTGGCAGGCCCCTGTAGGTGAATCACAGAAAAGACCTTTGGGATTTTG
    GAGCAAAGCTCTACCATCATCTGCAGACAACTATTCTCCCTTTGAAAAACAGCTCTTGGCCTGCTATTGG
    GCCTTAGTGGAAACTGAACGTTTGACAATAGGACACCAAGTTACTATGCGACCTGAACTACCCATCATGA
    GCTGGGTACTATCAGACCCTGCAAGTCATAAAGTGGGACGCGCACAGCAGCAGTCTGTTATCAAATGGAA
    GTGGTATATACGTGATCGGGCCAGAGCAGGTCCTGAAGGCACAAGCAAGTTACATGAAGAAGTTGCTCAA
    ATGCCTATGGTTTCTACTCCTGTTACACTGCCATCTGCTGCCAAACATGTGCCTATAGCCTCATGGGGTG
    TTCCCTATGATCGACTGACCGAAGAGGAAAAGACTAGAGCCTGGTTTACTGATGGCTCTGCACGTTATGC
    AGGCACCACCCAGAAGTGGACAGACAGCTGCAGCATTACAACCCCTTTCTGGGACAACCCTGAAAGACAC
    AGGTGAAGGGAAATCTTCACAGTGGGCAGAACTTCGGGCAGTACACATGGTATTACAGTTTGTTTGCAAG
    AAGAAATGGCCAGATGTACGATTATTCACTGACTCATGGGCTGTAGCCAATGGATTGGCTGGATGGTCAG
    GGACTTGGAAAGATCACAATTGGAAAATTGGTGAGAAAGACATCTGGGGAAGAAGTATGTGGATAGATCT
    CTCCAAATGGGCAAAGGATGTGAAGATATTTGTGTCCCATGTAAATGCTCACCAAAAGGTGACTTCAGCT
    GAGGAGGAGTTCAATAATCAAGTGGATAAGATGACCCGTTCTGTGGACAGTCAGCCTCTCTCCCCAGCCA
    TCCCTGTCATTGCTCAATGGGCACATGAACAAAGTGGCCATGGTGGTCGAGATGGAGGTTATGCTTGGGC
    TCAGCAACACGGGCTTCCACTCACCAAGGCTGACCTGGCTACAGCTGCTGCTGATTGCCAGATCTGCCAA
    CAGCAGAAACCAACACTGAGTCCCAGATATGGCACCATTCCTCGAGGTGACCAGCCAGCAACCTGGTGGC
    AGGTTGACTACATTGGACCACTTCCTTCGTGGAAAGGACAGCGTTTTGTTCTTACTGGAGTAGATACTTA
    TTCTGGTTATGGATTTGCCTTTCCTGTACGTAATGCCTCTGCTAAAACCACCATTAACGGACTGACAGAA
    TGCCTTATCTATCGTCATGGTATTCCACACAGTATTGCTTCTGACCAAGGAACTCATTTCACAGCCAGAG
    AAGTACGACAGTGGGCCCACGATCATGGAATTCACTGGTCTTACCACATTCCCCATCATCCTGAAGCAGC
    TGGTCTGATAGAAAGATGGAATGGCCTTCTGAAGACGCAGTTACAGCGCCAATTAGGTGGTAACAGCTTG
    GAAGGCTGGGGTAGAGTTCTTCAGAAGGCAGTATATGCTTTGAATCAGCGCTCGATATATAGTACAGTTT
    CACCCATAGCCAGGATTCATGGGTCCAGGAATCAAGGGGTGGAAAAAGGAATAGTTCCACTTACTATCAC
    TCCTAGTGACCCTCTAGGAAAATTTTTGCTTCCTGTCCCCATAACTCTAGGTTCTGCTGGCTTAGAAGTT
    TTGGCTCCAGAGAGGGGAGTGCTCCTACCAGGAGCTACAACAAACATTCCATTGAACTGGAAGCTCAGAC
    TTCCCCCTGGTCATTTTGGGCTTCTAATGCCCTTAAACCAACAGGCTAAAAAAGGAGTAACAGTGTTAGG
    AGGGGTGATAGATCCAGATTACCATGGGGAAATTGGATTACCTCTTCACAATGGTGGTAAGCAAGATTAT
    GTCTGGAGTGTAGGAGATCCCTTAGGGCGTCTCTTAGTACTACCATGTCCTGTGATTAAAGTCAATGGGA
    AACTACAACAGCCTAATCCAAGCAGGATGACAAAGGACACAGACCCATCAGGAATGAAGGTATGGGTCAA
    TCCTCCAGGAAAAGAGCCAAGACCTGCTGAGGTGCTGACTGAAGGAGAAGGAAATATAGAATGGGTAGTA
    GAGGAAGGTAGTTATAAATACCAATTAAGGCCACGTAACCAGTTGCAGAAACGAGGATTATAAAGTAATA
    TGAATGCCCATTGTAAATTTACTAATGCGTTTGCGATTGTACGAGGGATAGTTATATCATGTTAGGCGTA
    TTTACAAACTTGTTATTGTTTTATGTGAACATGAGATATTATTTGTGTCAAGTTGACAAGGGGTGGATTG
    TAGTGGCTATTCCTGGTTGTCAACTTGACAATATTTGGAATGAACTACAATCCGGAATTGGAAGGCTCAC
    CAGTGACCCTTATCTGGAGGCTTGGAGATCCTTATCTGGATCTTGGTTTGAAGATCTTGAGCCATAGTGG
    CTATGGATTCCAGAAGATTGAATCTCCGAGTTTAAGGAACACACCTTTAATCTGGGCTACGCCTTTCATC
    TGGGATTAAAGGTGTGGCGGAACACACCTTTAATCTGGACTACACCTTCTGCTGGAGACAATATAAGGAC
    ATTGAAAGAAGGGAGTCTAGCTCTTGCTCTTGCTCCTTCGCCTGCTTGCTGCGTGAGACTGAGTAACTAC
    TAGATCCTTGGACTTCCATTCACAGCTGCGACTGAACAATTGTTGGGAATTGGGCTGCCGACTCTAAGTC
    ATCAATAAATTCCTTTACTATCTAGAGACTATCCATAGTTCTGTGACTCTAGAGAACCCTGACTAATACA
    TCCCTACATACAGGAAACTTGATGTATAAGTAAAGAAAATAGTAAATCTAAAAATTTCCTTATCAAATAC
    ATGCAAGAAATCCAAAATACCATGAAAAGACCTGATCTAAAAATAGTAGGAACTGAAGGTGAAGTGTCCC
    AGCTCTGAAAACTAGAAAATGTTTTCAATATTTTTCCTAACAGTGAAGACATGGATCTAATGAGGCCACC
    TCTTATAGCCATGCAAGACTGACAGTGGAGGGATAAGGACACCAATCCACCCACAAAACTTTTGACCCTA
    AATCAGTTTTATCTAAAAGCAATGCAGGGGCACAAATGGAGCAGAGACTGGAGGAATGGTCAAACAATAA
    CCTGTCATATCTGAGACCCACCTAATTGGCATACACCAGTCACTGACATTATTAATAATGTTCCATTATG
    CTTACAGGCATTTCTCTAGCATTACTATTCTTGGAGAGACTTCACACAGCATCTTATTGAAACAGATGCA
    GACACCCAGAACCAAACATTGGATGGAGATTGGGATCCTTAAAGAAGAGTTGGGAGGATAATTGAGAGAC
    CTCAAAGGAATAGCAACCCCATAGAAAGACACGAACAGGGTCAGTAAACCTGGACCCATGGGGTATCTCA
    GAGACTGATCACCAACCAAAAATCACAGAGGGCCTGGATTGATTCCCCTGGCACACATGTAGCAGAGGTC
    TGCCTTGTCCTTCAGTAGGTGAAGATGAGCCTAAGGCTTCAGAGACTTGATATATCAGCATACAGCAACA
    CCCAAGTGTGTCCCACTATCTCAGAGGTGAAGGGGTGGAGATGGGCAGAAGGGTCCTGATAGGGGACAAC
    TGCAAAGAGGCAATATTTGGGACAGAAAGAAAGGAAGAGAGAGGAAGATAAAGAGAGAGATGAAGGAAGG
    AAACAAACAAACCAAGATGAAGAGAGAGAAAAGGGGGAAAATAGCCTTGAATGGTTCAGGGATTCAAAGG
    GACATACCTAAGCATGGTAAAACAATGCACATAATGGCAGCAAGTAGCTAACACTGAATTAAATAGAAAG
    ACACATAAAGCAGTTCTACTAAAGTAAGAGACAGAGTTGCCCAATCTCACCCTATTTATTCAATAATAAT
    GTACTTGAAGTTCTAGCTAGGGCTGTAAGACAACTCAAGGAGATCGGAGGATACAAATTAGAAAGAAAAA
    TTCAAAGAATTGTAATTGGTAGATGATAGGATAATATACATAAATGACCTCAAAATTCTTCCAGAGAACT
    CTGAAAGCTGATAAATACCTTCAGCAAAGTGGCTAGAAACAAAATTACTTCATAGAATTCAGGAGCTATC
    CTTTATAGAAAAGTTAAAGTGGCTGAGAAAGAAATTAGGAAAATCACATTCTTTGCAATAACCAAAAATA
    ATATGAATTAGCTTGGTGTGACTCTAATCTTGCAAGTGAAAGATGTGTGTGACAAGAGCTTCAGGACCCT
    GAAGAAAGAAATCAAAGAACTCAAAGATGCAAAGTACTCTAATGCTCATGGATAGGCAGAATTAACATAA
    TGAAAATGCCAAATTTAACAATTCAATCTACAGATTCAGTGGAATTCCCATTAAATATCCAACCCAATTT
    ATTACATTCTTGAAAAAGCAAATCTCAACTTCATATAGAAAAACAAGAAATTGAGGGTAGCTAACAAAAT
    CCTGAACAATGAAAACACTTCAGGAGAATTCACCATCCCCTACCTCAAGCTGTATTTTAGAGCAATAGTT
    ATTAAAACTGCATGGTATTTGTATAGAAACAGATATGATGATCAATGTAATTGAATTGAATACACTGACA
    TAAAACCACACTGTTATGGACACTTGATTTTTGACAAAGAACCCAATAATCATAATAAAAATCATAATAA
    GAATGCATCCCCCAACAAATGGTCCTGATCTAAATGCAAATAGATTCATATCTATCATCCTGCACGAAAT
    TCAAATCAAAGTGAATTGCAGACTTCGACCTAATACTGGATTAACTAAATCTAAATGAACAAAAAGTAGA
    GAATAGTTTTGAACTCATTGATGCAGGATTCAATTTCCTGAACAGAACCACAATGGCTCAGGCTCTAGGA
    TCATAAATTGGTAGATAGGATCTCATGAAACTGAAAAACTTCTGTAAGGCAAAGGCAATAAAACAAAATG
    GCAACCTACAGATTGGAAAAAAAATAATCTTCAGTATCCCTAAATCCCATTGAAGGCCAATATGCAAAGT
    ATATAAAGAACTCAAGATGTTATCCTCCACAAAACCAAATAAATCAATTAAAAATGAACTACAGAGCTAA
    CAAGAGAATTCTCAACAGAGGAATCACCAATGACTGAGAATCACTTAAAGAAACATTCAATATTTGTAGT
    CACCAGAGAATTGCAAATCAAAACTACCCTGAGATTCTACTTTATACCAATCATAATGGTCAAGATAAAA
    ATTCAAATGACAGCGCATGTTGGTGAGGATGTGTATACTTTTGCATTGCTGGTGAGGAAAACAATCTGGC
    AGCTCCTCAGAAAATTGTAAATAATTCTACCTGAAGATCCAGCCATACCACTCCTGTGCATATACATAAA
    ATGTGCTCCACCATACCACTAGGAGATATGTGCCACTATGCCCATAGCAGCCTTATTTGTTAATAGCCAA
    AAGATGGATACAACCCTGATGTGCCTCAAACAAAGATTGTATATAGAAAATATGGGTTCCCTTACACAAT
    GGTATTCTACTCAGCAATTAAAACGTGAGAACATCATAAAGTTTTCAGGCAAACTGATCAAATGAAAAAG
    TATAATCTTGAGTGAGGTAACAGAACCAAAATGACCTGCATGGGATGTACTCACTGGTAAGTGAATATTA
    GACTAAAAGTATAGAATATCAATGATGAAAGCCACAGACCATAAAGAGTTTAATAAGATGGAAAGCTCAA
    GTACGGATTCTTCAATCCAATATAGAAAGAGGGACAAAATAATCAGGGGAGGCAGAGGGAGAGAGAGACA
    TTTGGTGGAAATGGGAGAAGAAGGGAGAAAGGCAGAAAGGATCAGGCGTTGGGGAACACTGGAAAGCAGC
    CCAGGGGTCCTGGTAAATGGATTAAATATTCAGCTGAATGGAGGTGGGAGGCAGGGGGAAGCTCTGCAAA
    GTCCAAGAGACCTGGGATGTGAGAGGCTCCCCAGATGATAATCTTAGCCTTCATGCCTAACAGTTGTAGA
    TAAACCCTGAAGAGATCACTTCCAATAGATGCAGAGGGCCCTAAGTGGTTGGATGGAGTCCCCCAACTTA
    CCTCAAAATTGTCAATACTCATAGAAATTAGGACAATGAAAATCAAAACACCCTGAGATTGTATCTTATG
    TCTGTCACAATGGTTAAGACCAAAACCTCAAGTGATGGCTTGTGCTGGCAAAGATTCAGAATAGTAAAAG
    TCTCCCCATGGCTTGTGGGAATGCAAACTCTTACAACCTCTTTGGAAGTATATTTGATTGTTACCTGGTA
    TAAAATGGCAAAAAAAAAAAATGGTTGAAGGGGGACTAAAAAAGGAAGAAAGGGGAGAACTATGGGATGC
    GAAACAAGAAAGTTTGTTGCAAAAGAAATATGTTTCCACTGCAAACCCTGAGTCTCAGACAGAAGGGGAC
    CTGGAATTCTTCAGATACAAAGAATCTCTAAACCCTGAGGACATTCTATCACAAATAAGTAAAATTCAGA
    AAATTCTGAGTGCTCCCATCACGGAGATGAATCTGCTATGAACAGCTCATAGGTGTGACCCTCTACAAAA
    GCCATATTATTGAAAAGCCACATTGTGCCCAGACTTTGGAAAGACTGAGCTCATATCCTGAAATACAGTT
    ATGTGTGGTTCTATTTAATTACACATTTACACTAAGAAAACATGGCAGTATGGGAATGAAGCTTGTTCTG
    TACACATTAACAGAGGGAAACTAAACAAAGTATGGTGAATCCCTAACCAAAAGTAAAAAAAAAAAAAGAA
    AGAAAAGAAAATAAAAGTGAAACTACAATATGTTTCAAATGCTGTAACTGAAATCTGGTTTTTTGATGCT
    TATATCTGGTATCATCAGTGACTTCAGATTTAGTCCAACTCCAGAGCATGGTATAGCAGAAAGACATGCA
    AATAAGCCTTCTCTCTGCCCATGAAAAACACCTCGGCCCTGACCCTGCAGCTCTGACAGAGGAGGCCAGT
    CCTGGATTCGATTCCCAGTTCCTCACATTCAGTGATCAGCACTGAACACGGACCCCTCACCATGAACTTG
    GGGCTCAGCTTGATTTTCCTTGTCCTTGTTTTAAAAGGTAATTTATTGAGAAGAGATGACATCTGTTGTA
    TGCTCATGAGACAGAAAAATTGTTTGTTTTGTTAGTGACAGTTTTCCAACCAGTATTCTCTGTTTGCAGG
    TGTCCAGTGTGAAGTGAAGCTGGTGGAGTCTGGGGGAGGCTTAGTGCAGCCTGGAGGGTCCCTGAAACTC
    TCCTGTGCAACCTCTGGATTCACTTTCAGTGACTATTACATGTATTGGGTTCGCCAGACTCCAGAGAAGA
    GGCTGGAGTGGGTCGCATACATTAGTAATGGTGGTGGTAGCACCTATTATCCAGACACTGTAAAGGGCCG
    ATTCACCATCTCCAGAGACAATGCCAAGAACACCCTGTACCTGCAAATGAGCCGTCTGAAGTCTGAGGAC
    ACAGCCATGTATTACTGTGCAAGACACACAATGAGGAAATGTTACTGTGAGCTCAAACTAAAACCTCCTG
    CAGAGCACCCAGGACCAGCAGGGGGCGCAGAGAGCACATGGAGTTCTGATTCACAGAAGAGTTACAGCCT
    GTACAATTAGACCCAATCTTCAACAAACCGTCAAAATATTCGATCCAAAATTGTTCCTGTCTAAAAGTAA
    TTCAAGGACAAAATGGACCAGAGACTGAAGAAATGGCTGACCTGTGACCCTCCCAACTTTGGATCTATCT
    CATAGGCAGGTACCAAACCTTGACATTTGTCACTGACACTGTATTGTGCTTGCAGACAGGAGCATAGCAT
    GGCTGACCTCTAAGAGGCTCTGCAAGCACCTGAATGAGACAGATGTAAATAGAGTGTACAACTGGATTAA
    GTTTGAAGACTGCAATGGAAGAGTTAGAGGAAGGAATGAAAAATCTGAAGGGGATCACAACCCCAGAAGA
    AGACCAACAGTGCCAATTAAACTGGATGCCTGGGAACTCCCAGAGACTAAGCCACAAACCAAGAATCATG
    CAGGCTGGTCTGAGAATCCTGGCACCCAAGTCTCAAGGAACTGCCTTTTCTTGGCTCAGATGGGAGAAGA
    TGAGCCTAAAGCTTTAGACTTGACGCCCCAGGGATGGGCAATACAAAGTTGAGTTTCTTGGGAAAGTGAA
    GAGGATGGTGGGAGGAGGAATAAATCTGGGAAGTGGGACTGGTTGGGGACAACATATTGGTCCTAAATTT
    ATGAAATAATTATCTAATTGATAAAAAGAGTCCTTGGGGTAATGGAGGGCTAGACTCCTCTGTGCCTAGT
    TTGTAACTCTACAGGGATCCTCTTTAAAAGAATAGGGTGCACATAGAGTATATGTGTGTGACACTAATAC
    AGGGGTAAGTGTTTCTGTAAGAACTTTATGAATAAACTTTATTAAAACATCAAAAAGTATAGGTTGTAGC
    AACCCTTGACCTGTACGAATGTTTATAAAACTTTCTATTTTCCTTAATTATATCTGTTTTGCATTTGTTT
    ATTTATTTATTTACTTACTTACTTATTTATGATTTCACTGTGTCTTTCTGTAGTCCTGTATGTGTTTATT
    TGTCTCTTTATTGCTCTGTTTCTGTTTCTTTCTCTCTGTCTAGTATTGTATCTCTCTGTGTCTCTATGTC
    GCCGATTGTGTCTGTGTGTATGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGCATATTGAAA
    TGAGATCTCTTCTTCTATCAGTGTACATAATGACTTTGAAATAAAGTCCATCACTGGGCTTGGATATCAC
    TATCTTGTTAGAATGGTTGCCCAAAGTGTTCCAACCATCACACTGTTTCTACATATAATAGATGGGTTTA
    TTGATTTACTACCAAAACTACCCCATCTTAAGTTATGGATATTAAACACAGATCCTCATGGTGTGTTAAG
    AACTTGAAGCACAGAGCTATATGTACAGCCCACTAAAAATGACTTAAATATAAGATAAACTCTGGCTTGA
    ACAAAACACAGAGCATCACACGAGGCAGAAGTGAATCTCTATGAGGACCAGGATCACATCCCAAAGAACC
    AAAGAACACTTGAGACTGTGGAACCCTAGAGTCAGGGCTGACACTCAGTAAGATTTACTTCATAGAGCAT
    GATGTGGGATTCAAGAAGAAATCAGGCAGGGCCTGTGACCCATGAACCAGATGACTTCCAGTCTCTCCAT
    CATCCTCACACAAACCATAGGCAACAGCTCAGCACTGACTCACCTGTGATGCTGGTGACAAAATGTGTGC
    AAAGCCTCAGAACTGAGACGTGAGGCCAATGTTGCTACCGACACTCAGTGAGCTTCAATTTGCTGCAAAC
    TGCTCCAAAACAACTCAAAGGGTAACTTCTTCTTTTTCTATTTGTACTTGTGATGCCTTGGTAGATATAG
    TTCCCCAATAATTTAATAGGACAAATCATTTTTCCTTTTAACACATTAATCCCCTTTCCTTCCCCCAAGA
    TTCTAAAATTTTTCTTTAACACTGATGTCTGAGAGATATGGCATAATAGATGTTTGTCTTATTCTGAGTT
    GTTCCTTATCAAAAGAAATCAGCTGTGGCACTTTGAACCTAAATATAACAATATTTCACAAAGGCATTCT
    GGGAATATATAGATGGTATTGCTACAAAAGAATAGGAGGATCTATGGCCATACCACCCTTAATGAACCAG
    ATACTATCTAAAAGATTAGGACAGCTGGGCATGTTGGCACAGGCCTTTAATCCCAGCACTAAGGAGGCAG
    AGGCAGGCAGATTTCTGATTCGAGGCCAGACTGGACTACAAAGTGAGTTCCAAGACAACCAGGGCTATAC
    AGAGAAACCCTGTCTCGAAAAAACAAAACAAAACAAAACAAGAGTAGGAGGGTATTAGATGCGAGGTGAT
    GATGGCCATTCAATCAAACCAGAATGTGACCTGAGAAAAGGTCTAAGTTTGTCAGCTTGTCCTGGAGATG
    TGTTGCCTCTGATAAATGCAGAGCTGGAACTGCAATACATTGGATTCCTGTGAGTTACGGAGAAATAAAA
    GGAATAGCCTCTGTTTCCTTTGGTTCATCAAGTTGGCAGTGAGCTAGAAGATGATACTGGGAACCATCAC
    ATGTACTTCTACAGAGTTATTCTACATTCTACAAGTCAGTCTTGCTTGCTTTCGTTTCTGTGAGGAGCTA
    AATACAGAATGTTTTCAATGTCTCATAATGTTCTGTGCACACCCATGGGTGCCTAGCCAAGGATAGAAAC
    TTGTATCTGATAAGGAAAGAGGATGCTGCAGTGGCCACACTCTGAGATCACCTCCTGCCAAATTATACTA
    GAGTGTTTTACATAGTCTTGAAAACACTAGGTCAAATATGTTGTCATCCAGATATGAAAACTCTGTGCAA
    CAATTCAGAAATACAGTGGTCAGGACAACTGGTATGTAACACTTTAGTTCCAGCCCACATTAATCTCACA
    TCTTTTCTGTGGTTTCAATAAAGAGCACACATGTTTGGAACACCATCTCCACTTTGTATGCTTATCCTTA
    TGCATCAAACTTTTCCTGTAATTTCCTACCCCGCACAGGTTCCTGTCTTGATCTCTTTTTCTAATGAACA
    GCAATACAGAAGTGTTGGCCAAATGAACACTTTCACCCCAAGTTGCTTTGCCATTGTGTTTCATCACAGC
    ATTAGTAACTCCCAGTAAGGCTACTGGTTACCCTGCATCTTCTATGTAGATCTTTTGATGAAGTTCCAGG
    CTTGGGGTCTTTATCTGACTGTTATCCTGGTTAATTCATGTCCACCAATAGAATATTGTTCTCATTTTCA
    ATATCATATGAAGTTACCTGTTTATAGGATCTTCCTAAAGCAGAAAACTATATAAAATGTCTGCTTACTT
    TAAGAAAAGTATGTGTCCTTGGAGGTAAATGGAGGAAAGGGTGGAGGATGTTGAGTAATGGAAGACTGGC
    TAATACAGGAAGGTCACAGAATTGAATGATTTTAAAAATTTTAACTCCTCATCAATGAGGTACTTCAAGT
    TGAGGCAGGAGTCCTTGATGCACAGGTGACCCAAAGGCCCCAGCCTCTGTTTCTTGGTCTGCTCCAGTCT
    CCCGGCTCAGCACAGTTCACTGAGTGACAATCTTTAAGATAGTCTTTCAGGATACAGTTATCACAGTTTT
    CAAACTCTCTTCATTGAAACAATATAATGAGTCAGAGTCCAGTGTGCCATTAATAGGCCCTATGCAATAG
    GATTTTACTTCATCTGTGGAAAGAAACCACCATGGCCTCATCAAGGCCTCATTTGATGATTAGTGTAGAA
    AGCGTCCCCAGAGCTTTGCTGGGATGAAAACCCTGGCAAGATGTTTAGGGCACTCTCCATCTGACAGGAC
    AATTCTATCAAGGGTTGCTTCCATATAGAGAGAAATCTCCACATCTGCAGTATTTCCCGATTTATCAACA
    GTTCTTTACCCCGTGTCATATGCATAAAATCTTTTCTCTGTAGAATTTTCAGTACTAAAAACTAACAAGG
    ATGTTGGTCCTGATATCAGACATAATAAATAAATAAACATCAAATTATACCCTAAACATGTGGAGATGGT
    TTTCTGTTATGAATTTATTGGCTCTCTAAAAAGTGTTAATTAAGCCAGGCGTGATGGCACATGCCTTTAA
    TCCCAGCACTTGTGAGGCAGAGGCAGGCGAATTTCTGAGTTTGAGGCCAAACTGATCTACAGAGTGATTT
    CCAGGACAGCCAGGGTTACACAAAAAAACCCTGTCTCCAAAAAGTAACAAAAAGAAAGTGTTAATTAACA
    TCTACACTTTAAGATAATTTGGTGGCAAAGGTTAATAGTCTGAAATACTAGATATGAAAGTATGACACCT
    AAATTGCATGCAGAGAATAAAGCTGAATTCCAATGAGATTCATGCCTTGTGAATCCATTCCAATCTGATC
    TCAATCTTCAAACATGTTTGTGCATAATTTACATCTTAATCAGTTGCTGGAAATTAAAAGGACATAAGCT
    AAACTTAAAACTCTTTCTATTTAATGTGTCAGAATAGAATATGTGCACTGAAGTTTTCATGTGCATAGGA
    TATCATTGTTACAATGATGGTTCAAATACGCACCAGTAGCACAGGTGATGCTTGACATGAAAAAAACTGT
    GACCAGAGCCCAGACGTTGATGTTGGCTGAAAGAGCCTAGTGTCTCACATTTGATCAAGCAAAGTGTTAT
    TCAGAGAAGCAGTGCCAGATTTGGGATCCTTCTTAATGGATCAAGAACATGAGGAAGATTTGGAAGCCAG
    ATTGATGAGATTACTAGAATCCTGGATCTGAACACACAACACACAATAGTAAGTTGAACTTTTCCACGCA
    ATGCTAAAGATAAAGCATCCAGTATCATGTTATACAGGACCAAGGTGAGGATCAGTCTGTGGGTGAAGTA
    CAATGAACTGGAAATTGTTTGGATTTTAAATGTTGGTTTTTAAATTATATATAAAATATATATATATATA
    TATATATATACATATATATATATATATATATATATATATATATATCGGAACCAACATTTAAAATTTGGAT
    TTTAAATGTTGGTTTTTAAATTATATATAAATTATATATATATATATATATATATATATATATATATATA
    TATATATATATATATCGGAACCAACATTTAAATTCCTAATTCTTAAGGACTTCACTTTTGACCAAAAATA
    TTTGAAATGGGTTATTTAGGTCTGTGGTGGTTTGAATATGCATAGCCTATAGGAAGTGGAAGTATGGCCA
    TTTTGTAGTATGTGTAGCCTTGATGGAGGAAGTACATCACTATATGGTGTTGTGAGAGTTGAGATCCTAT
    GTTCAAGTTCTGCCAAAAACAGAAGAGAGTCCCCTCCTGGATATTTGAAACAGATGCAGAGGCCCAAAGC
    CAAACATTGGGTATATCTCAGGGTTTCTTATGGAAAAGTTGGCTGAAGGATTGAAGGCCTTAAAGGGGAT
    AGGAACTTCACAGGAAAACCAACAGATTCATCTAACCTAGACTCTAGGGGTCTTTCAAAGGTTGAGTCAC
    CATACAAAAAGGACACAATGGCTAGACCTAGGTCCCTGATACATATGTAGCAAATGTGCAGCTTAGACTC
    CATGTGGATTCCCCAACGACTAGAGCAGGTATTGTCCCTGAAGTTATTGCTTGTCTGTAGAATACATTTC
    CCAACATAATTGTCTTGTCTGGCCTCAGTAGGAGAGTATGTTCCAATCCTGGAGAGACTTGATATGCCAG
    GATTGAGAGATTAAGGGTCTCCCACCATCTCAAAGTTCATGGGTATGACAGGGGAGGGGCAGTGCAGGTT
    TTCCCCATCTCTGATTTCCAGCATTTGCACCCCCAATATTGAGGGGGAGGTCTAGCAATTGGAGGGGGGA
    CAAACAGTATGAGAAAGCTAACTTTAGTGGTGTTGTCACAGTGTGGGGTATTGTGGGTGGGAGTGGAGAT
    GAATCCTCCTCCTCCTCAGGAGGCTGTAGCAGGTGCTTGCCCTCTTTTGGGACAGTAGAGCTGTGGTCAG
    TACTGGCCTGTTCCTGACAAATTTATTCTGTGCTGTGACCATTTATTCAAGGGAGGAAGATTTAAGACTT
    GCTATGATAACCTGACGAATCTGGACAAACAAGAGACAGGAGGTAACACCTGAGTTACTCTTTTGCTTGC
    TAGTACAGAAGAGCACTATAATCCACAAATTGGGGTCCCACATATTCTTGAGTGGGATCCAAGGTGCCAT
    AATTTCAGCCACATTCCAAAGTCCCTCAAGGTCTGACAGTTTAGTCTTTAGGCTTCTCCTAACCAAATCA
    TATTTGGAGTTCTTTAACATAAAAGGGTAGTTTCCCCATATCACTGCCAGCAAAACAGGTTGAATTTGGA
    CAGACAAGCAAAACTATCACAAACAAGACAGACTATGTGTGCGATCCAAATGTCTTGTGATTAGAGGGGA
    AGTTCTGCAGCTTATTAGGCTGTGTCCTTATGCCCACAAATGTCTTCAGATAGGAAAGGGCCATTGGGTG
    CCAATCCTTAGTTCTTCTGTTTCCTGGGCTGTCAGTTTTTATGTGGAGAAGACATGAACCAAATGCAAAG
    TCATGTATCCTACAAGAACTGACATACACAGACAAACAAGGAATAACAATGAGCTCTCTCATTCACCTAA
    GGGGGTCTTATAACATAGAACAGAAAGGGGCCAACTTAGCAAGAATTGACCAAAAGGTGGTCACCTAGAC
    CACACCACAATGCAGGAAGGATATCAATGAAGGAAGAACAAAGGAAAGGCCAAATCAAGTTTGTTGGCAC
    ATGACATAAAACAGTGCTCAAAAAACAATAGATGCGAGCAAAATGAAGCATTGGAATCATATCGGGGTAC
    ATAGGGGTCACTCTTACCCCTGTTCAAGTGCCAGATGTTGTTTTAGCCTTAGGCTCCCTGAGTTTGTCTT
    TAGGGGAAATGGGTAAGAATACACAAAAATAATGTCACAGAATCTTAGAGGCAGATGAGAAGTCAAAGCA
    GACTCATTTATTGCTATAGAAAAGAATGCCTTTATACCTTCTGTCCATAACACCTCTGCCCATATATGCT
    CATCTCTGTGAGGCAATGGACTACCTGCAGACAGGCTGGTATCCAGTCAAGCTGAGGTCTGAACCACAAT
    GGTCGTAACTCACCTAAAGGACGTGGTAGGCATGACGCGATAGGCGTTCCCTCATGCTCCTGGAACTCCG
    GCCCCTGCCTAAGGTACCACCTCCCACAGCCCCCACAAGAGAAGCATGGTCAGTAGTCATGTAAGCAATG
    GCCCAAGCTTCTGACCTTCAGCCTAAACTCCTCCCCAGTTACCTAGCAACAGTGAAGACCATAAAATGGG
    ATGTTAGGCCCCCACCTCACTCTCTTACTCCTTTGTTCCTTTACCTCTCACTTCTCTCAATTCTCTCTCC
    TCTTCCCTTTCTTTGTCTTCTTCTTTCCTTGTCTCTCTGTCTTTCTCTTTCTCTCTAGCCTTCTCTGCCT
    CTCTCTCTCTCTCTGTCTCTCTGTCTCTCTCTTCTCTCTTTCCCTTGAATTTCTTTTTTTCTTTTTTCTT
    TTTTTGATGAGCACAGTATAAATAGTTTATTGCATTGTTTCTGAATGTGGCTGTATTCTCTATTGTTCTC
    TTTCTTATTTTTTTTCTTTTTTTGGTTGTTTTTGTTTTTATAGTCTCGCACAGAATTCTACATCTACCAA
    ATCCCCATTGTGTACTTTAGTTTTGTCTTGTATTCAAAGGTTCTTTCAGAAAGAATCTTAAAGATGAAAT
    TTGCCTTCCAACTTTTCAAAAATACATATAAAGATAGATGTTACATAGTTCACGGAATAGACACATATAC
    GGAGATGCAGCAATATCTCCTTTGTGCCTCTTGTATATTCATGTTATTTCCTCAACTAAAAATACATAGC
    CACAAAGACATACAATGAGCACTCCACTTAGGAAAATATGGCCATATTTTTTTACATTTTTATGATTTTA
    TGATTAGGTATATTCTTCATTTACATTTCCAATGCTACCCCAAAAGTCCCCCAACCCTTCCCTCACTCCC
    CTTCCCCACTCCCACTTGTTGGCCCTGGAGTTCCCCTGTACTGAGGCATATAAAGTTTGCAAGACCAATG
    GGCCTCTCTTTCCACTGATGGCCCACAAGGTCATCTTCTGATACATATGCAGCTAGATACATATACATAC
    ACGAGCTCCAGGGGGTACTGGTTAGTTCATATTGTTGTTCCACCTATAGGGTTGCAGATCCCTTCAGCTC
    CTTGGGTACTTTCTCTAGCTCCTCCATTGAGGGCCCTGTGATCCATCCAATAGCTGACTGTGAGCATCCA
    CTTCTGTGTTTGCTAGGCCCCATTATAGCCTTGCAAGACAGCTATATCAGGGTCCTTTCAGCAAAATCTT
    GCTAGTGTGTGCAATGGTGTCAGCATTTGGGGGCTGATTATGGCATGGATCCCCGGATATGGCAGTCTCT
    AGATGGTCCATCCTTTCATCTCAGCTCCAATCTTTGTCTCTGTAACTCTTTCCATGGGTGTTTTGTTCCC
    AATTCTAAGAAGGAGCAAAGTGTCCACACATTTGTATTCATTACTCTTGAGTTTCATGTGTTTCCCTTGC
    ATTTCTATAATAAACCATAAGGAGTCTCTGCTCTACCAAGACCCGCTGCACACTCTGGTCAGTGTTGGGA
    ACTTTTCCCCTATTCCCTCTCTCCTATAACTCCGGGGCTACAGGGTGTCTCCTTTGGGTCCCGGTTGGGA
    GCTGTCTCTTCTCAACCCCCTGACTCATGGGTCAGAGGCCTAAATCTCCACCCAAGGCTGTGTGAAAAGC
    ACCGGGTGGTCTCCCCATATCTCCCTGTCCAGAGCACAGGAACTCTGGCCGGACATGGCATATTTTTCCT
    CCCCAACTTCTTCCCCGGCCTCCTCAGGGCTGTCCCTTCATTTTGTTCCCCACACATCTCCACATGGCTG
    CCACCATCCAATTGGCTGCTGAGGTCACACACTCTGTCTTTGTTCTTCTCTGAGTCTCATGCAGGTTTTG
    TGTTAGTAAATGCAAAAGTGCCTGCTGTGCATGCATGAACCATTACAGGCTGCTAGGCAGAACATGCTGA
    CTTGCTCCTGGATTATAAATCCATCACTGTGATAGCAGGACATATCCAGAAGACATTATTTAACAACACT
    CCTCTTCGTGCTCAACCTCTCATGGTCTTTCTACCTCCTCTTTCTTAGTGTTCTCTGAGCCTACATGAAA
    TGTGAACAAACCTGAAAAAAATCTCTGTGTCAAATACATAGTGTGGATTGGGAAGGAAAAACCCTGCACT
    TGTGTGTGGGCAGGGAAATGCTGGTGCTTTAACAGGACAAGTGCGGTGTGGCTAGAGAAAGTGATGAGAA
    GAAGGGAAGCATGAGAACTGGGTGGGTGGATCCCATGTCTACTGAAAATGCTATGTTGATGTCAAGATAT
    TGTGTCTTGTTACAAAAATTCATTGAGTACCTAGGTTATTCTCAGTATATAAAAGGGGAGGAATGAAACT
    AGAATTAAACACACACACACACACACACACACACACACACAAACACACACACACGAGTAGAGAAAAGAAA
    TAGTCATGAGTTGCCTAGTGAATGAAGAGCGGAAAATGGTGCAGTTAATAGGGATCATAGAAAGAACTGG
    GGGATGCACACGAATGGGTTTCCTGTAATTATGTCTTCATAGTAATCTCTGCTCAATAATCAGACAGTGA
    CAATGTATGCCTCATTTACAAGCCCTGATGGCCTCTCAGAGGAAAGCATCTCTCTGAAATGAATAAAGTT
    CAGAAATGTCCTAAGTGTCCCTGTCACAGGAAAGCAGTGTTGGTAACGTTTCCAGGAAGCTCAGTCTTTG
    TCAAATATCCACAACAAGAAGAAGCCATGTCTAGACAGACAACAGACTGGGAAAGACTGAGCTCATGTAT
    GGAAACACAACTATGTGTCATGCTTTTATTTTCACATTATACTGAGGGGATATGACATTATAGAAACACA
    GTTTGTTCTTTGCATATGCTGAGAGAGGAACTAGATGAAGTGTGCTAATTCTTAGCAATAAAAAGATATA
    CAAAGTGGTACTTTACTGTTTCAATTTTTGTAACTGGCATCATTGTCTTTGATATTTTATATCTTCCTTG
    AGCACTGCCTTCTCTCAAGTGTCCAACTTCAGAGTATGCTATAGCAGGAAGACTACCAAATAAGATTAAT
    TTTTTTGTACCCATGAAAAAATTATGTGCCCTGACCCCTGTTCTCTGAAAGAGGAGCCAAGTTCTGGATT
    CCCAGATCCTCATATTCATTGATCAGCAGTGAACACAGATCATTCACCATGGACATGGGGCTCATCTGGA
    TTCTCCTTATTGTTTTTAAAAAAGGATTTCATTGGGAAAAGCTGCCTCATATTTCTATGACCAGGAGAGG
    AAGATACAGCTAGAGACACAAGCCCCACCATGTAAAATCTGTATGGTACTCTCGTTTTCATTTTACAACA
    TTTTGCTTTTGCATTGCAAAGGAGCAATAAGGGTTCAGCAATCAGCACTGTAACTGTACTTTTAAAATTT
    CCACCTCTACCCTCTGTGTCCTCTATCTAGTGATAGAAAGTGAAATAAGCACATAAAGCATGGGACAAGA
    AGAACACACAGAGGAGCAGAGACTGGCTACAAGTGGCAGCCAGCATGGAGCTGGACAGAATTTAAAAAGA
    TAAAGAGAAATGTCATGGCATGAAGCAGTGACTTTTTCTGTTCACAATGCCTGCAAAAACTTTATGGAGC
    CTACTACTGCTGAGATATGCAGGTTTGGTTCCAGAGAGGATTTTCTGTTTTATTTAATTTGCTTTTAAAT
    TTTTCTTCTTTGTATAGTCTGTATTTTTAAAAAGGGGTTGAATGAATACCTAAGCAGTTGGAAAATTTGT
    GAGTAGAAACCGAGGGCCTGAGAAACAAATAAATCAAAATTTTGAAATGGCAAAAGAAAGGGTTCATTCT
    ATTTTCTCTTTTCAGAAAAGGTTGCAAAGTTGGATGTGCAAATGGAGATGTTATGGGTGGACTTGGAACA
    TCTTGGGAAGGAAGGAACCCAGGAAAAGAAAGAATGAAATGGCTCAGCCTCAATGACTGAGCAAGAGAGT
    TAGAGTCACCCACAGGAGAAAAGAAGAAAATAAACAGCACTGGGGTGAATTTGGGTCAGAGAAAACCTTA
    AAATGCCAGAGGACAATGTGATGAAAGAGACCATTTGAAAGAAAGGGTTAACCTCATTCCATCAGTCATG
    CCAGAGTTAGAGAATGGGCAGTCTGGAGTTACAAGATCACGATTAGCCTTCCCAGTATGTATACAGCATA
    TTCCTGATAATGAGATGAAGCAAAGTTTGACAAGGTAAGATTGTATCCTATAGTAATATATAGATCAAAG
    GCATGTTGCAGTAAATCTCCAACAGAAATAAGCCCGGGCAATGAAAACACAACTCAATTAATATGAATAC
    GTGCTGTGCACCTAGACTGGGCAGATCTACCACTCCACTACCATATGAGAGATCCCTTATAACTTGTGGT
    TTCTCCAGGCCAGCTGCTTCTGCTCTACTTTCCTTCCTCCTCCTCCTATGTCATCCTCTCCCTCACTCTT
    TCTCTCCCAAAACTTTCAGCTGCACCTTCCCCTCTTCATCCCCCAATCAGTGGCTCTAGCCTTTATTTAT
    AAATTAAGGTAGGAAGAAGGTTTATAGGAAATTACCTGAGTGTTGACGTGTTGATAACCCCACACAAGAG
    AACAAAATTAATATCAAATATGATTAGCTCCAGGGTTATATGCAACAAAGGCATGATAAAGTGGTCATGA
    TTTCATATGAGATGTACTGGACTCATGTGAAAAAACGTTTAAATACATGGGCTTACTCAAAATATAGACT
    CATACCCCCAAGATGGGAAGAGACTGGTAACATTTGTACTGGAGGCTGGTCTGCTGTGGCAGCCATTAAC
    ACAGTGGAGGGAAGAGCCTCAAAGAGTGAAATAGAGGAAGGGGAACAAATACAGTAAACCACCAGTTACT
    ACTTAAAGGGCAGTGTTCTGATGTCCTAGGGAGGGCACTCCAAAATACCAATGGCCTTATCCTTAAATTT
    ATTGTTTAATGAGCCTACACTGATCTCAGTGGCCCACTACTAAGGAGAAATGACAGGCACTTGAACAGCT
    GATATGAGAACAGCTGGAGGCACAGTATACAGAAGAGTTTACAAGCCTATGGAACTCCCCTGTATTTTTT
    TATGATGAGGAAATCTGAAAAATGTAAAATGTTGAAAGATTTAAGAGCAGTTATTAGAGTAGATCAACCA
    ATGAGTCTCTTGCAGCCTGGAATTCTTTTATCTTGTTTGTAACAACAATCAGGCTCCATAAATTATAAAC
    TATAAAAATTTACTTTATAAATTATAAATATATATATATGTGTGTCTGTAGATAGATAGATAGATAAATA
    GATAGATAGATAGATAGATAGATAGATAGATATATGGATTTGATGGTTGCAGCAAATTCTAATTGGTTCC
    AACAACCCTACTCACATAATACATTCATACAGGTTTGATAGATGGAGCTAAGTTTTAAATAAATTATTTT
    TCTCCCATGGCTTATATATACACCACCAAAATTCTCAAAAATTAAAATGTGATTGTGTTGTATTTTTCTT
    TTACTGAATGACTATAAAAAGTTACAACATTCTCCATAAATTTACATGAAAAAATATTATGTAGTGCAGG
    TAAAGAAAACAAATTGACCCAAGAATGGTGTATATTCATTACTAAGCAACTTTTTAGATTCACAAAGTGT
    GGGTAAACAAGGTAATTTTTTCAATCAGTTTTTTTTAACTGGCAGGCAGCAATTCAGAGTTACAATGAGA
    AGATTAATAATTTTATTGTGTATTTTAAAATAAATCTTACAAAAATATTAATAGAATCACAAATTTATAC
    CTTTGTATAAAAACAATCAGTCATTTCTACTTTAAGAAACAGAACTCACATCTACTCATCAATCATTTTA
    TTAAGTCATATTACAAAGCTGAGTGCTAACATGGGTATAAGAAAACCATAACCTTATTCACCAGCCCAGC
    GTCAAAAAGAAAAAAACCAGTCATATCAGCTGCTGCTTCAAGAGTTCTTGTTCCTTGACATTAACAAAAT
    CCCTAGCTTAACTATTAAATTTTTTTTCAAAACTTCTAATTGATCCCTTAGATAAATGTTTGTGCTAACC
    ATCGGGACACATCCCATGAGTTCTGAAGCAGTGTGTTGTTCTTCATGCATGGCCCTTTTGTAGAGCTGTG
    AGTGTAGGGGAAGAGGGGGGAGAGAGAGCCCGTGTCCAGCCAGAGATCCTGTGCTCTGGGCAGGCAGACA
    CGGGAGGACAACGGAACACTTTTCACTCGGCCTTTGGTGGGCATCTGGCTGTGTGAAGTTACTGACCCCA
    CATGGTGGGGGATGGACAAGGGGCAGCCCCTGGTACCAGGAGCCCCAGGGCTACACTCTCGGCCCCAGAT
    ATACAAGAAGAGGGCAGAGGGAGAGAGGCTCCCACACAGGCGAGAGTCCTTAGTCTGGTCTGTGGCTGGA
    GCAGGGGAATTCCTTCTGATTGGAGATTAGGCACAGCTGATTAGGGGAAAGCCTACCCCATCATCCAAGC
    ACAATGGACTTTGAGGAACAGAGCCAGTCTAAGCTTTTATAGCTTTATGGTAGAAAGGCAGGGAGAAAGG
    AGAGAATGTGGAGAGAGACAGAGAGAGACTGGCCATGGCCAAGAGGAGGGAAGGGGGAAGAGAGAGAAAC
    AGGAAAAGCTAGAAAGTAAGATAAGAGAAAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGCAAAGTG
    GGGCCAAGCAGCCCCTTTTCTAGTGAGCTTGTCATCTCACAGTTGCTAGGTAACTGGGGAGGAGTTTAGT
    CTGAAGGTCAGAAGCTTGGGACCTTGTGTATGTGACTACTAACCACAGCTTCTCCTGTCGGGACTGTGGG
    AGCAGTAACTTTGACAGGAGACAGGGATCCAGGAGACATGAGGGAACACCTTCTGTCCCACATAGGTGGA
    ATCGGTTGTACCAGGGTTCAGAACTCAACTCCACTGGAGACCAGCCTATGTGTGCATAGCCCATTGCCCT
    ACAGCCTTTGACATTCTACAGAGTTCTGAGACTGGTAGAGATACAAAATAGCTAGGATTACACAGAGAAA
    CACTGGCTTGACAATAAAACTTCCAAAACAAATATAAATGAATAAATACACAAATTGGAGCAAGTGAACT
    TGCACTAAATCCATCAAAACTTGCACAGGATGGCTGTCTCCATAATGTTCAGATCTACTTCTATTAATGT
    CATTAAGAAGACAAAGATTATGCACAAAAAGAAACAAAACAAGAAACCCAAAAGGTAAAGGCTCCAATTG
    TAAGTAATAGACCCACAGTCTCTGAGGCCTGACTGTGCAGGTCCTCACCTTTGGTAATCAGCACTGAATG
    CAGACCACTCCTCATGGACTTTGGGCTCAGGTTTGTTTTCCTTGTCCTTATTTTAAAAGGTAATTCATAG
    AAATGAGATCCTGCCAGTATTGTGTACATGAGAAATAGAAAAATTGGTTTTCTTTGCTCTATTTTGTTTT
    GTTTGGTTAATGACAGTTTCCAAATCAGCATTCTTTGCTTTGAGGTGCCCAGTGTGAGGTGAAGCTGGTA
    GGGTCAGGGCAGCCTGGAGGGTCCCTGAAACACTCCTGTGCAGCCTCTGTAGTCACTGTGAGTGACTACT
    GAATGACCTGGGTCCTTCAGGCTCTAAAGAAGGGGCTGGAGAGGGTGGAAATAATTTTTAATGGTGGAGG
    TAGCACCTATTATCCAGACACCATGAAGGGCTGATTCACCATCTACAGAGATGATGCCAGAAACACACTT
    TACCTGAAAATAAACAGTCTGAGGTCTGAGTACACAGCCATGTGTGTGTGTGTGTGTGTGTGTGTGTGTG
    TGTGTGTGTGTGTGTGTGTGTGTGAGTGTGTATTCATATATATATATATAGTGTGTATGTATATTCATAT
    ATATATGTATATTCATAAGGTTGAGTAAATGGACTTAAACTGATTCCATCACAACTTCCATGGGATGGAT
    ATTTCCCAGTGTTAAGACCTGTCAACATCACTGTCATTCAGGAGACAATGATTATGCACAACAAAACAAG
    AAACCCAAAAGCAGAGGACTCCAATTACAATAGACCCAGACCCACAGTCTCTGAAGATTGACTGTACAGT
    TCAACCCAGCCCTGTACTTCTCTTCCCTAGAATTTACATTACTGAGTAACTGAGGAAAGCTCTACAATAT
    CTGTTCTCTATAGTGGTCAACACCTCCAAACACAGGTTACCCATATTCATGCCTGCCTTCTGCTACACTT
    CTTGCCATAATGTAGACTACTTCAGCCTATTTTGTACTCCAGTTAACGAAACTCAAGACTAGCTGCATGT
    TAGTCCTTATTCTGAAATATTATGAACAGGTGACCTCCCATCATTCACCAATGCAATAATCATATTTAGG
    AATATGAGGTTTTATGAGATATAAGCACAAGGGAGAGAAAGTAAGAAAACTACATAGATATATAGACTGA
    CATAAATCAAGACTTGCATGAGCTAGTGCCCAAGTACCATGTCCCTAAGTGGCAAGGAGTATCTTTTGAG
    CCTAGTGAGATGAGGTACAAATCGGACTCTTACATCTTTTTAGATAAACATGTGAGATCAATGGACTAAA
    GGCGTGAGCTGGGCTTCCTTGCAATCCATTTTCCATACAAGATAACAATAGATCTGGCTCCACAGACACG
    ATGAGAATAGTCTTAATTAGTTCTTTAAGTAGAATGACTGATCACTAAGAGCCCAATTCCATACTAAATA
    CTCTTCTGGATTATGCACAGATAAAAATTGCACATAGGGCATGGGGCACTGATCTCCCTGCACTACATGA
    ATGGGGGCTCATTTACTAAATGTTCCCATGTTTCTTCCTAGTGCTGCACAGAGCAAATCCTACAACTTCC
    TGCTTGTCTACAATGTAAACTCCAGACAGTACCAGAAAATCATTCCTTATGTTCCTCTCCAGGTGCTTCA
    ACAAGCACAGTGCAAATTTCTGTCACCCTG
  • Molecule Role : Vaximmutor
  • Additional Molecule Role : Vaximmutor
  • Related Vaccine(s): Bordetella pertussis aroA mutant vaccine
IV. Vaccine Information
1. Actacel
a. Product Name:
Diphtheria, tetanus, acellular pertussis, Haemophilus influenzae type b conjugate vaccine
b. Tradename:
Actacel
c. Manufacturer:
Sanofi Pasteur Ltd
d. Vaccine Ontology ID:
VO_0010705
e. Type:
Subunit vaccine
f. Status:
Licensed
g. Location Licensed:
Canada
h. Host Species for Licensed Use:
Human
i. Adjuvant: aluminum phosphate vaccine adjuvant
j. Preservative:
2 phenoxy ethanol
k. Immunization Route
Intramuscular injection (i.m.)
l. Storage
Refrigerate at 2° to 8°C.
m . Approved Age for Licensed Use
2 months to 7 years
n. Description
Products: Proteins + Conjugate.
2. Adacel
a. Product Name:
Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine, Adsorbed
b. Tradename:
Adacel
c. Manufacturer:
Sanofi Pasteur, Ltd (USA: License #1726)
d. Vaccine Ontology ID:
VO_0000005
e. CDC CVX code:
20, 115
f. Type:
Toxoid vaccine
g. Status:
Licensed
h. Location Licensed:
USA: License #1726; Canada
i. Host Species for Licensed Use:
Human
j. Antigen
Pertussis
k. Adjuvant: aluminum phosphate vaccine adjuvant
l. Preparation
Clostridium tetani is grown in modified Mueller-Miller casamino acid medium without beef heart infusion. Tetanus toxin is detoxified with formaldehyde and purified by ammonium sulfate fractionation and diafiltration. Diphtheria and tetanus toxoids are individually adsorbed onto aluminum phosphate (FDA: Adacel).
m. Immunization Route
Intramuscular injection (i.m.)
n. Storage
Adacel vaccine should be stored at 2° to 8°C (35° to 46°F). DO NOT FREEZE
o . Approved Age for Licensed Use
Adacel vaccine is indicated for active booster immunization for the prevention of tetanus, diphtheria and pertussis as a single dose in persons 11 through 64 years of age.
p. Contraindication
A severe allergic reaction (e.g., anaphylaxis) after a previous dose of Adacel vaccine or any other tetanus toxoid, diphtheria toxoid or pertussis containing vaccine or any other component of this vaccine is a contraindication to vaccination with Adacel vaccine (FDA: Adacel).
q. Description
It is a sterile liquid suspension of tetanus and diphtheria toxoids and acellular pertussis components adsorbed onto aluminum phosphate, for intramuscular administration.
3. Adacel-Polio
a. Product Name:
Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed Combined with Inactivated Poliomyelitis Vaccine
b. Tradename:
Adacel-Polio
c. Manufacturer:
Sanofi Pasteur SA
d. Type:
Toxoid vaccine + Subunit vaccine + Inactivated or "killed" vaccine
e. Status:
Licensed
f. Location Licensed:
Canada
g. Host Species for Licensed Use:
Human
h. Preservative:
2-phenoxyethanol
i. Allergen:
Neomycin, Polymyxin B, Streptomycin
j. Immunization Route
Intramuscular injection (i.m.)
k. Storage
Store at 2° to 8°C (35° to 46°F), do not freeze.
l . Approved Age for Licensed Use
4 years and older.
m. Description
ADACEL®-POLIO is a sterile, uniform, cloudy, white suspension of tetanus and diphtheria toxoids and acellular pertussis vaccine adsorbed separately on aluminum phosphate and combined with inactivated poliomyelitis vaccine (vero cell origin) types 1, 2 and 3, and suspended in water for injection. Acellular pertussis vaccine is composed of five purified pertussis antigens (PT, FHA, PRN and FIM). (Product Monograph: Adacel-Polio)
4. B. pertussis BrkA protein vaccine
a. Vaccine Ontology ID:
VO_0011377
b. Type:
Subunit vaccine
c. Status:
Research
d. Antigen
B. pertussis brkA
e. Gene Engineering of brkA
  • Type: Recombinant protein preparation
  • Description: Fraction BS was applied to a Mono Q Sepharose (Amersham, Biosciences) (0.5 mg protein per ml resin) previously equilibrated with 25 mM Tris–HCl, pH 8.0. Proteins were eluted with a NaCl gradient (0–1 M) in 25 mM Tris–HCl, pH 8.0, in 0.5 ml fractions at a flow rate of 1 ml/min. Elution was monitored at A280 nm. The fractions showing the same peak profile were pooled and eluted again under the same chromatography conditions. Samples were submitted to sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) (T = 12.5% in 0.75 M Tris, 0.2% SDS, pH 8.8) and electrophoresis was performed at 60 mA in 25 mM Tris, 0.192 M glycine, 0.1% SDS, pH 8.3. The gel was stained with silver nitrate and fractions showing a similar molecular mass profile were pooled, concentrated by centrifugation at 440 × g in Centrifugal Ultrafree-20 tubes, 10 kDa (Millipore), and their protein concentration was evaluated. Four pools were formed (P1, P2, P3, P4), and used for immunization of mice (Cainelli et al., 2007).
  • Detailed Gene Information: Click here.
f. Immunization Route
Subcutaneous injection
g. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: Female BALB/c mice, 4–6 weeks old (Animal House of the Instituto Butantan) (9–15 mice/group) were subcutaneously injected three times at weekly intervals (days 0, 7, 14) with BS pools (P1, P2, P3, P4) (1 μg/0.1 ml/mouse), and two times (days 0 and 14) with 73 kDa or 60 kDa proteins (1 μg/0.1 ml/mouse) alone or mixed with Diphtheria-Pertussis-Tetanus (DPT) vaccine formulated without aluminum hydroxide (NA-DPT), (2 μl/mouse), (Instituto Butantan). Current DPT vaccine containing aluminum hydroxide (DPTBut) was used as control (2 μl/mouse) (Lot no. 0008147/0 and 0309132, Instituto Butantan). Non-immunized mice (injected with physiologic saline) were used as control (Cainelli et al., 2007).
  • Challenge Protocol: Animals were challenged by intracerebral route (i.c.) with live B. pertussis (strain 18323, NIH, USA), 21 days after the first immunization. Each mouse was inoculated with 30,000 live bacteria. Deaths were recorded until day 15 (Cainelli et al., 2007).
  • Efficacy: High levels of antibodies were induced, and a 78% protection rate of mice challenged with live B. pertussis was observed. The 73 kDa N-terminal alpha-domain of BrkA autotransporter protein, one protein identified in the fraction, stimulated antibodies against pertussis and induced a 42% protection rate against the challenge (Cainelli et al., 2007).
5. B. pertussis Cpn60 protein vaccine
a. Vaccine Ontology ID:
VO_0011357
b. Type:
Subunit vaccine
c. Status:
Research
d. Antigen
B. pertussis cpn60/60 kDa chaperonin
e. Gene Engineering of Cpn60
  • Type: Recombinant protein preparation
  • Description: Fraction BS was applied to a Mono Q Sepharose (Amersham, Biosciences) (0.5 mg protein per ml resin) previously equilibrated with 25 mM Tris–HCl, pH 8.0. Proteins were eluted with a NaCl gradient (0–1 M) in 25 mM Tris–HCl, pH 8.0, in 0.5 ml fractions at a flow rate of 1 ml/min. Elution was monitored at A280 nm. The fractions showing the same peak profile were pooled and eluted again under the same chromatography conditions. Samples were submitted to sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) (T = 12.5% in 0.75 M Tris, 0.2% SDS, pH 8.8) and electrophoresis was performed at 60 mA in 25 mM Tris, 0.192 M glycine, 0.1% SDS, pH 8.3. The gel was stained with silver nitrate and fractions showing a similar molecular mass profile were pooled, concentrated by centrifugation at 440 × g in Centrifugal Ultrafree-20 tubes, 10 kDa (Millipore), and their protein concentration was evaluated. Four pools were formed (P1, P2, P3, P4), and used for immunization of mice (Cainelli et al., 2007).
  • Detailed Gene Information: Click here.
f. Immunization Route
Subcutaneous injection
g. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: Female BALB/c mice, 4–6 weeks old (Animal House of the Instituto Butantan) (9–15 mice/group) were subcutaneously injected three times at weekly intervals (days 0, 7, 14) with BS pools (P1, P2, P3, P4) (1 μg/0.1 ml/mouse), and two times (days 0 and 14) with 73 kDa or 60 kDa proteins (1 μg/0.1 ml/mouse) alone or mixed with Diphtheria-Pertussis-Tetanus (DPT) vaccine formulated without aluminum hydroxide (NA-DPT), (2 μl/mouse), (Instituto Butantan). Current DPT vaccine containing aluminum hydroxide (DPTBut) was used as control (2 μl/mouse) (Lot no. 0008147/0 and 0309132, Instituto Butantan). Non-immunized mice (injected with physiologic saline) were used as control (Cainelli et al., 2007).
  • Challenge Protocol: Animals were challenged by intracerebral route (i.c.) with live B. pertussis (strain 18323, NIH, USA), 21 days after the first immunization. Each mouse was inoculated with 30,000 live bacteria. Deaths were recorded until day 15 (Cainelli et al., 2007).
  • Efficacy: High levels of antibodies were induced, and a 78% protection rate of mice challenged with live B. pertussis was observed. The Cpn60/60 kDa chaperonin, one protein identified in the fraction, stimulated antibodies against pertussis and induced a 42% protection rate against the challenge (Cainelli et al., 2007).
6. B. pertussis CyaA protein vaccine
a. Vaccine Ontology ID:
VO_0011359
b. Type:
Subunit vaccine
c. Status:
Research
d. Antigen
B. pertussis secreted adenylate cyclase (cyaA)
e. Gene Engineering of CyaA
  • Type: Recombinant protein preparation
  • Description: The AC was purified from culture supernatants using a camodulin affinity chromatography. The preparation consisted of two polypeptides of 45 and 43 kDa that are structurally related as described by Ladant et al (Guiso et al., 1989).
  • Detailed Gene Information: Click here.
f. Adjuvant: aluminum hydroxide vaccine adjuvant
g. Immunization Route
Subcutaneous injection
h. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: For active immunizations, Balb/c mice were given, subcutaneously, 3,ug of purified AC adsorbed on aluminium hydroxide, three times, at one week intervals . The mice were bled 5 days after the last injection in order to assess the presence of circulating anti-AC antibodies . The lethal challenge was performed 9 days after the final injection (Guiso et al., 1989).
  • Challenge Protocol: Bacterial suspension (50 pl) was injected intranasally to groups of 10 3-week-old female Balb/c mice (CERJ, St Berthevin, France), weighing 16±1 g . The LD 50 for the challenge inocula was determined daily by recording the number of dead mice . Pulmonary edema was quantified by lung weight (Guiso et al., 1989).
  • Efficacy: Active immunization with purified B. pertussis secreted adenylate cyclase (cyaA) protect mice against a lethal respiratory challenge with B. pertussis or B. parapertussis (Guiso et al., 1989).
7. B. pertussis DNA vaccine encoding Prn
a. Vaccine Ontology ID:
VO_0011391
b. Type:
DNA vaccine
c. Status:
Research
d. Antigen
B. pertussis pertactin precursor prn2
e. Gene Engineering of Prn
  • Type: DNA vaccine construction
  • Description: To construct a prn mutant, amplification of the region containing the whole prn2 gene of the CCHMC1 strain was performed using PRN-F GGCACAGGACCGGCGCGTGTTTCGCGCACGACTCT) and PRN-R (CGCGTGGTGCGCCTGAAAGGCGGCGATGCCTTCA) with attB adaptors. The PCR products were cloned into pDONR221 to obtain pDONR-PTXA1 and pDONR-PRN2 by site-specific recombination techniques using the Gateway cloning system (Invitrogen). The regions transferred into the pDONR221 plasmid were sequenced for verification. pDONR-PTXA1 or pDONR-PRN2 was mixed with pABB-CRS2 to obtain pABB-PTXA1 and pABB-PRN2 by using the Gateway cloning system. pABB-PTXA1 or pABB-PRN2 was introduced into E. coli SM10pir and mobilized into the B. pertussis strain Tohama by conjugation (Komatsu et al., 2010).
  • Detailed Gene Information: Click here.
f. Vector:
DONR221 (Invitrogen, Carlsbad, CA) and pABB-CRS2 (Komatsu et al., 2010).
g. Immunization Route
Subcutaneous injection
h. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: 3.5-week-old female BALB/c mice (Japan SLC, Hamamatsu) were immunized by two subcutaneous injections of 0.25 SHDs (0.125 ml) over a 2-week interval (Komatsu et al., 2010).
  • Challenge Protocol: Two weeks after the second immunization, 50 µl of a suspension containing approximately 6 x 106 CFU of B. pertussis was instilled intranasally into mice anesthetized by intraperitoneal injection with pentobarbital sodium (Nembutal; Abbott Laboratories, Abbott Park, IL). Two hours (day 0) or 2, 5, or 8 days after the challenge, the mice were euthanized by pentobarbital injection (Komatsu et al., 2010).
  • Efficacy: While the vaccine was effective against all of the B. pertussis strains regardless of the allele expression pattern, the strain expressing ptxA1 and prn2 displayed a survival advantage over the other strains (Komatsu et al., 2010).
8. B. pertussis DNA vaccine pcDNA/S1
a. Vaccine Ontology ID:
VO_0004545
b. Type:
DNA vaccine
c. Status:
Research
d. Host Species as Laboratory Animal Model:
Mouse
e. Gene Engineering of S1
  • Type: DNA vaccine construction
  • Description:
  • Detailed Gene Information: Click here.
f. Vector:
pcDNA.3.1(+) (Kamachi et al., 2003)
g. Immunization Route
Gene gun
h. Mouse Response
  • Vaccination Protocol: For immunization, 0.5 mg of gold particles were coated with 2 μg of plasmid DNA and 0.5 mg gold per injection was used. Mice were immunized intradermally three times on days 0, 14, and 28 using a Helios Gene Gun at a helium gas pressure of 400 psi (Kamachi et al., 2003).
  • Immune Response: Gene gun vaccination was employed for the delivery of pcDNA/S1, and the induction of IgG1 predominant antibody production was observed (Kamachi et al., 2003).
  • Challenge Protocol: Immunized BALB/c mice were challenged intranasally with B. pertussis strain 18–323 (Kamachi et al., 2003).
  • Efficacy: In the pcDNA/S1-immune group, five out of 10 mice survived 24 hours after the challenge, whereas all of the mice in the pcDNA-immune group died within 24 hours (Kamachi et al., 2003).
9. B. pertussis FhaB and 69 kDa OMP protein vaccine
a. Vaccine Ontology ID:
VO_0011498
b. Type:
Subunit vaccine
c. Status:
Research
d. Antigen
Combination of the B. pertussis 69-kDa outer membrane protein and filamentous hemagglutinin (fhaB)
e. Gene Engineering of FhaB
  • Type: Recombinant protein preparation
  • Description: A crystal clear supernatant of 5-day-old static cultures containing proteolysis inhibitor was purified. To remove impurities, the FHA was precipitated by overnight dialysis against 25-30 volumes of buffer A at 4 C, and the precipitate was collected by centrifugation. The precipitated FHA was dissolved in the smallest possible volume of 40 mM B-alanine buffer at pH 3.5, clarified by centrifugation, and applied at room temperature at a flow of 30 ml/h to a Superose 12 column. The retained highly purified FHA was eluted (Novotny et al., 1991).
  • Detailed Gene Information: Click here.
f. Adjuvant: Alhydrogel
g. Immunization Route
Intramuscular injection (i.m.)
h. Mouse Response
  • Vaccination Protocol: Groups of mice were injected intraperitoneally with 0.5 ml volumes of four concentrations (Novotny et al., 1991).
  • Challenge Protocol: Mice were challenged intracerebrally 14 days after antigen injection. The challenge dose contained 300-400 LD50, and a 1:1250 dilution of the challenge does contained ~ 10cfu. All mice were challenged within 90 minutes after the challenge suspension was thawed; the challenge was injected using a 1 ml syringe in a Hamilton PB600-I dispensor that reproducibly delivers 20-ul voumes (Novotny et al., 1991).
  • Efficacy: A combination of the 69-kDa outer membrane protein and filamentous hemagglutinin (fhaB), both isolated from lymphocytosis promoting factor (LPF; pertussis toxin) minus mutants of Bordetella pertussis, is protective in the mouse intracerebral challenge potency (Kendrick) test (Novotny et al., 1991).
10. B. pertussis PTx protein vaccine
a. Vaccine Ontology ID:
VO_0011361
b. Type:
Subunit vaccine
c. Status:
Research
d. Antigen
B. pertussis pertussis toxin (PTx)
e. Gene Engineering of PtxE
  • Type: Recombinant protein preparation
  • Description: Vaccine is prepared by chemically modifying purified PT from culture supernatants with tetranitromethane (TNM). The lot was adsorbed to aluminum hydroxide (Alhydogel; Superfos, Vedbaek, Denmark) at a concentration of 50 μg of protein adsorbed to 4 mg per 1.0 ml. Animal doses (2.5, 0.5, and 0.1 μg) were prepared by making fivefold serial dilutions in aluminum hydroxide (4 mg/ml) diluent and given in a volume of 50 μl (Bruss and Siber, 2002).
  • Detailed Gene Information: Click here.
f. Gene Engineering of PtxA
  • Type: Recombinant protein preparation
  • Description: Vaccine is prepared by chemically modifying purified PT from culture supernatants with tetranitromethane (TNM). The lot was adsorbed to aluminum hydroxide (Alhydogel; Superfos, Vedbaek, Denmark) at a concentration of 50 μg of protein adsorbed to 4 mg per 1.0 ml. Animal doses (2.5, 0.5, and 0.1 μg) were prepared by making fivefold serial dilutions in aluminum hydroxide (4 mg/ml) diluent and given in a volume of 50 μl (Bruss and Siber, 2002).
  • Detailed Gene Information: Click here.
g. Gene Engineering of PtxB
  • Type: Recombinant protein preparation
  • Description: Vaccine is prepared by chemically modifying purified PT from culture supernatants with tetranitromethane (TNM). The lot was adsorbed to aluminum hydroxide (Alhydogel; Superfos, Vedbaek, Denmark) at a concentration of 50 μg of protein adsorbed to 4 mg per 1.0 ml. Animal doses (2.5, 0.5, and 0.1 μg) were prepared by making fivefold serial dilutions in aluminum hydroxide (4 mg/ml) diluent and given in a volume of 50 μl (Bruss and Siber, 2002).
  • Detailed Gene Information: Click here.
h. Gene Engineering of PtxC
  • Type: Recombinant protein preparation
  • Description: Vaccine is prepared by chemically modifying purified PT from culture supernatants with tetranitromethane (TNM). The lot was adsorbed to aluminum hydroxide (Alhydogel; Superfos, Vedbaek, Denmark) at a concentration of 50 μg of protein adsorbed to 4 mg per 1.0 ml. Animal doses (2.5, 0.5, and 0.1 μg) were prepared by making fivefold serial dilutions in aluminum hydroxide (4 mg/ml) diluent and given in a volume of 50 μl (Bruss and Siber, 2002).
  • Detailed Gene Information: Click here.
i. Gene Engineering of PtxD
  • Type: Recombinant protein preparation
  • Description: Vaccine is prepared by chemically modifying purified PT from culture supernatants with tetranitromethane (TNM). The lot was adsorbed to aluminum hydroxide (Alhydogel; Superfos, Vedbaek, Denmark) at a concentration of 50 μg of protein adsorbed to 4 mg per 1.0 ml. Animal doses (2.5, 0.5, and 0.1 μg) were prepared by making fivefold serial dilutions in aluminum hydroxide (4 mg/ml) diluent and given in a volume of 50 μl (Bruss and Siber, 2002).
  • Detailed Gene Information: Click here.
j. Adjuvant: aluminum hydroxide vaccine adjuvant
k. Immunization Route
Intraperitoneal injection (i.p.)
l. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: Mice were removed from their cages, weighed, and placed on a stainless steel rack that fits inside of the Plexiglas aerosol chamber (40 by 40 by 40 cm). The 21-h culture of B. pertussis was suspended in sterile PBS to a concentration of approximately 2 × 109 CFU/ml of inoculum. This inoculum was delivered to the mice using a standard nebulizer (model 647; Devilbis, Somerset, Pa.) with a set pressure of 1.5 kg/cm2. The chamber and the nebulizer were enclosed in a biosafety level-2 hood and certified prior to use to document that airflow barriers were maintained. Uniformity of aerosol in the chamber was maintained with the use of two PABST 900 series AC fans (Newark Supply, Newark, N.J.). The even dispersion of the aerosol was confirmed with a light laser (Bruss and Siber, 2002).
  • Challenge Protocol: Mice were exposed to nebulization for 30 min and removed 30 min after termination of aerosol. The completion of the aerosol represented time 0. Mice were removed from the box and replaced into their cages. Cages were checked daily for mortality (Bruss and Siber, 2002).
  • Efficacy: BALB/c mice were immunized with PTx vaccine on day 6 of life and then challenged with B. pertussis using the aerosol challenge model. These primed mice were significantly better protected against leukocytosis, weight loss, and proliferation of B. pertussis in the lungs following aerosol challenge than the nonprimed group. This protection correlated with levels of anti-PT antibody in serum present on the day of aerosol challenge (Bruss and Siber, 2002).
11. Boostrix
a. Product Name:
Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine, Adsorbed
b. Tradename:
Boostrix
c. Manufacturer:
GlaxoSmithKline Biologicals
d. Vaccine Ontology ID:
VO_0000015
e. CDC CVX code:
20, 115
f. Type:
Toxoid vaccine
g. Status:
Licensed
h. Location Licensed:
USA (License #1617)
i. Host Species for Licensed Use:
Human
j. Adjuvant: aluminum phosphate vaccine adjuvant
k. Preparation
Tetanus toxin is produced by growing Clostridium tetani in a modified Latham medium derived from bovine casein. Toxins are detoxified with formaldehyde, concentrated by ultrafiltration, and purified by precipitation, dialysis, and sterile filtration (FDA: Boostrix).
l. Immunization Route
Intramuscular injection (i.m.)
m. Storage
Store refrigerated between 2º and 8ºC (36º and 46ºF). Do not freeze.
n . Approved Age for Licensed Use
BOOSTRIX is approved for use in individuals 10 through 64 years of age
o. Contraindication
A severe allergic reaction after a previous dose of any tetanus toxoid-diphtheria toxoid or pertussis antigen containing vaccine or any component of this vaccine is a contraindication to administration of BOOSTRIX (FDA: Boostrix).
p. Description
BOOSTRIX (Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine, Adsorbed) is a noninfectious, sterile, vaccine for intramuscular administration. It contains tetanus toxoid, diphtheria toxoid, and pertussis antigens (inactivated pertussis toxin [PT] and formaldehyde-treated filamentous hemagglutinin [FHA] and pertactin). The antigens are the same as those in INFANRIX, but BOOSTRIX is formulated with reduced quantities of these antigens (FDA: Boostrix).
12. Boostrix-Polio
a. Product Name:
Combined diphtheria, tetanus, acellular pertussis (adsorbed) and inactivated poliomyelitis vaccine
b. Tradename:
Boostrix-Polio
c. Manufacturer:
GlaxoSmithKline
d. Type:
Toxoid vaccine + Subunit vaccine + Inactivated or "killed" vaccine
e. Status:
Licensed
f. Location Licensed:
Canada
g. Host Species for Licensed Use:
Human
h. Allergen:
Neomycin, Polymyxin B
i. Immunization Route
Intramuscular injection (i.m.)
j. Storage
Store at 2° to 8°C (35° to 46°F), do not freeze.
k . Approved Age for Licensed Use
4 years of age and older.
l. Description
BOOSTRIX®-POLIO (combined diphtheria, tetanus, acellular pertussis and inactivated poliomyetitis) vaccine contains diphtheria toxoid, tetanus toxoid, three purified pertussis antigens [pertussis toxoid (PT), filamentous haemagglutinin (FHA) and pertactin (69 kDalton outer membrane protein)] adsorbed onto aluminum salts and inactivated polio virus types 1, 2 and 3. (GSK: Boostrix-Polio)
13. Bordetella pertussis aroA mutant vaccine
a. Vaccine Ontology ID:
VO_0002807
b. Type:
Live, attenuated vaccine
c. Status:
Research
d. Gene Engineering of aroA
  • Type: Gene mutation
  • Description:
  • Detailed Gene Information: Click here.
e. Preparation
A DNA fragment encoding a kanamycin resistance determinant was used to insertionally inactivate the cloned aroA gene of Bordetella pertussis in Escherichia coli K-12, and a conjugative shuttle vector system based on the suicide vector pRTP1 was used to deliver the mutations from E. coli back into B. pertussis CN2992FS and BP1. The aroA mutation was introduced by allelic exchange into the chromosome of B. pertussis, resulting in otherwise isogenic parental and aroA mutant pairs. The B. pertussis aroA mutants grew well on laboratory medium supplemented with aromatic compounds but failed to grow on unsupplemented medium (Roberts et al., 1990).
f. Immunization Route
intracerebral challenge
g. Mouse Response
  • Persistence: The B. pertussis aroA mutants expressed the normal B. pertussis extracellular, virulence-associated proteins (Roberts et al., 1990).
  • Efficacy: Mice exposed to three separate aerosols of live B. pertussis aroA bacteria were protected against lung colonization after being exposed to an aerosol containing the virulent parental B. pertussis strain. High-level antibodies against B. pertussis rapidly appeared in the sera of mice immunized by aerosol with the B. pertussis aroA strains and challenged with the virulent parent (Roberts et al., 1990).
14. Bordetella pertussis BPZE vectored vaccine
a. Vaccine Ontology ID:
VO_0004608
b. Type:
Recombinant vector vaccine
c. Status:
Research
d. Host Species as Laboratory Animal Model:
Mouse
e. Antigen
The pertussis toxin gene, which encodes a highly virulent toxin (Mielcarek et al., 2006).
f. Vector:
Bordetella pertussis BPZE, which is attenuated for 3 different toxins: the pertussis toxin, the dermonecrotic toxin, and the tracheal cytotoxins (Mielcarek et al., 2006).
g. Immunization Route
intranasal immunization
h. Virulence
The pertussis toxin itself if extremely virulent, but after thorough and careful attenuation, the virulence is basically gone (Mielcarek et al., 2006).
i. Description
This is an intranasal vaccine because pathogenic B. pertussis colonizes the respiratory tract of humans. The vaccine itself has been shown to only need one inoculation in order to elicit protection, making it a good candidate to be a vaccine vector for other diseases (Mielcarek et al., 2006).
j. Mouse Response
  • Vaccination Protocol: The mice were vaccinated with highly-attenuated B. pertussis in order to prepare for challenge with virulent wild-type B. pertussis (Mielcarek et al., 2006).
  • Vaccine Immune Response Type: VO_0000287
  • Challenge Protocol: After the mice had been inoculated with attenuated B. pertussis (which after a month had colonized the entire mouse respiratory tract) they were challenged with virulent wild-type B. pertussis (Mielcarek et al., 2006).
  • Efficacy: A single intranasal inoculation of mice with the B. pertussis vaccine vector induced the same level of protection, if not higher, as two injections of the commercial acellular vaccine (Mielcarek et al., 2006) .
  • Description: Inoculation with the B. pertussis vaccine vector shows protective immunity which rivals that of the vaccines currently on the market.
15. Bordetella pertussis dnt mutant vaccine
a. Vaccine Ontology ID:
VO_0002808
b. Type:
Live, attenuated vaccine
c. Status:
Research
d. Gene Engineering of dnt
  • Type: Gene mutation
  • Description:
  • Detailed Gene Information: Click here.
e. Preparation
his strain was obtained by genetically inactivating pertussis toxin via two point mutations in the ptx gene, by deleting dnt encoding dermonecrotic toxin, and by replacing the B. pertussis ampG gene by Escherichia coli ampG, resulting in the removal of tracheal cytotoxin (Feunou et al., 2008).
f. Immunization Route
intranasal immunization
g. Mouse Response
  • Persistence: The dnt mutant in B. pertussis yielded a highly attenuated strain that was still able to transiently colonize the mouse respiratory tract [Ref1805:Feunou et al., 2008.
  • Efficacy: A single intranasal administration of BPZE1(dnt mutant vaccine) induced full protection in adult mice (8 weeks old), as well as in infant mice (3 weeks old), whereas commercial acellular pertussis vaccine (aPV) only partially protected infant mice, even after repetitive doses (Feunou et al., 2008).
16. DAPTACEL
a. Product Name:
Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed
b. Tradename:
DAPTACEL
c. Manufacturer:
Sanofi Pasteur, Ltd.
d. Vaccine Ontology ID:
VO_0000029
e. CDC CVX code:
20, 106
f. Type:
Toxoid vaccine
g. Status:
Licensed
h. Location Licensed:
USA (License #1726)
i. Host Species for Licensed Use:
Human
j. Antigen
Isotonic suspension of pertussis antigens and diphtheria and tetanus toxoids (FDA: DAPTACEL).
k. Adjuvant: aluminum phosphate vaccine adjuvant
  • VO ID: VO_0000128
  • Description: DAPTACEL is a vaccine indicated for active immunization against diphtheria, tetanus and pertussis as a five-dose series in infants and children 6 weeks through 6 years of age.
l. Preparation
Clostridium tetani is grown in modified Mueller-Miller casamino acid medium without beef heart infusion. Tetanus toxin is detoxified with formaldehyde and purified by ammonium sulfate fractionation and diafiltration (FDA: DAPTACEL).
m. Immunization Route
Intramuscular injection (i.m.)
n. Storage
Should be stored at 2° to 8°C (35° to 46°F). DO NOT FREEZE.
o . Approved Age for Licensed Use
DAPTACEL is a vaccine indicated for active immunization against diphtheria, tetanus and pertussis as a five dose series in infants and children 6 weeks through 6 years of age (prior to 7th birthday) (FDA: DAPTACEL).
p. Contraindication
Severe allergic reaction (e.g. anaphylaxis) after a previous dose of any diphtheria toxoid, tetanus toxoid, or pertussis-containing vaccine, or any component of DAPTACEL, encephalopathy within 7 days of a previous pertussis-containing vaccine with no other identifiable cause and, progressive neurologic disorder until a treatment regimen has been established and the condition has stabilized (FDA: DAPTACEL).
q. Description
DAPTACEL is a vaccine indicated for active immunization against diphtheria, tetanus and pertussis as a five-dose series in infants and children 6 weeks through 6 years of age.
17. Infanrix
a. Product Name:
Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed
b. Tradename:
Infanrix
c. Manufacturer:
GlaxoSmithKline Biologicals
d. Vaccine Ontology ID:
VO_0000064
e. CDC CVX code:
20
f. Type:
Toxoid vaccine
g. Status:
Licensed
h. Location Licensed:
USA (License #1617 )
i. Host Species for Licensed Use:
Human
j. Antigen
Diphtheria and tetanus toxoids and 3 pertussis antigens [inactivated pertussis toxin (PT), filamentous hemagglutinin (FHA), and pertactin (69 kiloDalton outer membrane protein)] (FDA: Infanrix).
k. Adjuvant: aluminum hydroxide vaccine adjuvant
l. Preparation
Tetanus toxin is produced by growing Clostridium tetani in a modified Latham medium derived from bovine casein. The toxin is detoxified with formaldehyde, concentrated by ultrafiltration, and purified by precipitation, dialysis, and sterile filtration (FDA: Infanrix).
m. Immunization Route
Intramuscular injection (i.m.)
n. Storage
Store INFANRIX refrigerated between 2° and 8°C (36° and 46°F). Do not freeze.
o . Approved Age for Licensed Use
INFANRIX is indicated for active immunization against diphtheria, tetanus, and pertussis (whooping cough) as a 5-dose series in infants and children 6 weeks to 7 years of age (prior to seventh birthday). INFANRIX should not be administered to any infant before the age of 6 weeks, or to individuals 7 years of age or older (FDA: Infanrix).
p. Contraindication
Hypersensitivity to any component of the vaccine is a contraindication, the vaccine should not be administered to anyone with encephalopathy, progressive neurological disorders, or an allergic reaction to a previous dose (FDA: Infanrix).
q. Description
The vaccine is an noninfectious, sterile combination of diphtheria and tetanus toxoids and 3 pertussis antigens [inactivated pertussis toxin (PT), filamentous hemagglutinin (FHA), and pertactin (69 kiloDalton outer membrane protein)] adsorbed onto aluminum hydroxide (FDA: Infanrix).
18. Infanrix -IPV/Hib
a. Product Name:
Diphtheria, tetanus, pertussis (acellular component), poliomyelitis (inactivated) and Haemophilus type b conjugate vaccine (adsorbed)
b. Tradename:
Infanrix -IPV/Hib
c. Manufacturer:
GlaxoSmithKline
d. Vaccine Ontology ID:
VO_0010722
e. CDC CVX code:
120
f. Type:
Subunit vaccine + Inactivated or "killed" vaccine
g. Status:
Licensed
h. Location Licensed:
Canada
i. Host Species for Licensed Use:
Human
j. Adjuvant: aluminum hydroxide vaccine adjuvant
k. Preservative:
2 phenoxy ethanol
l. Allergen:
Polymyxin B Neomycin , Latex in plunger stopper of prefilled syringe
m. Immunization Route
Intramuscular injection (i.m.)
n. Storage
Store in a refrigerator (2°C – 8°C).
o . Approved Age for Licensed Use
2 months to 6 years of age.
p. Description
Products: Proteins + killed virus + conjugate. Other components: Formaldehyde Polysorbate 80, Lactose.
19. Infanrix-hexa
a. Product Name:
Combined diphtheria and tetanus toxoids, acellular pertussis, hepatitis B (recombinant), inactivated poliomyelitis and adsorbed conjugated Haemophilus influenzae type b vaccine
b. Tradename:
Infanrix-hexa
c. Manufacturer:
GlaxoSmithKline
d. Vaccine Ontology ID:
VO_0010719
e. Type:
Subunit vaccine + Inactivated or "killed" vaccine
f. Status:
Licensed
g. Location Licensed:
Canada
h. Host Species for Licensed Use:
Human
i. Adjuvant: aluminum phosphate vaccine adjuvant
j. Adjuvant: aluminum hydroxide vaccine adjuvant
k. Preservative:
2 phenoxy ethanol
l. Allergen:
Polymyxin B Neomycin, Latex in plunger stopper of prefilled syringe
m. Immunization Route
Intramuscular injection (i.m.)
n. Storage
Should be stored at 2° to 8°C (35° to 46°F).
o . Approved Age for Licensed Use
Under 7 years of age.
p. Description
Products: Proteins + killed viruses + conjugate. Other components: Yeast protein Formaldehyde, Lactose, Polysorbate 20 and 80.
20. Infanrix-IPV
a. Product Name:
Diphtheria, tetanus, pertussis (acellular, component) and poliomyelitis (inactivated) vaccine (adsorbed)
b. Tradename:
Infanrix-IPV
c. Manufacturer:
GlaxoSmithKline
d. Vaccine Ontology ID:
VO_0010721
e. Type:
Subunit vaccine + Inactivated or "killed" vaccine
f. Status:
Licensed
g. Location Licensed:
Canada
h. Host Species for Licensed Use:
Human
i. Adjuvant: aluminum hydroxide vaccine adjuvant
j. Preservative:
2 phenoxy ethanol
k. Allergen:
Polymyxin B Neomycin , Latex in plunger stopper of prefilled syringes
l. Immunization Route
Intramuscular injection (i.m.)
m. Storage
Store in a refrigerator (2°C - 8°C).
n . Approved Age for Licensed Use
2 months to 6 years of age.
o. Description
Products: Proteins + killed virus. Other components: Formaldehyde, Polysorbate 80.
21. Infanrix/Hib
a. Product Name:
Combined diphtheria, tetanus, acellular pertussis (DTPa) and Haemophilus influenza type b vaccine
b. Tradename:
Infanrix/Hib
c. Manufacturer:
GlaxoSmithKline
d. Vaccine Ontology ID:
VO_0010720
e. Type:
Subunit vaccine
f. Status:
Licensed
g. Location Licensed:
Canada
h. Host Species for Licensed Use:
Human
i. Adjuvant: aluminum hydroxide vaccine adjuvant
j. Preservative:
2 phenoxy ethanol
k. Allergen:
Latex in plunger stopper of prefilled syringe
l. Immunization Route
Intramuscular injection (i.m.)
m. Storage
Refrigerated stored between +2°C and +8°C.
n . Approved Age for Licensed Use
15 months and older
o. Description
Products: Proteins + conjugate. Other components: Formaldehyde, Lactose.
22. KINRIX
a. Product Name:
Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed and Inactivated Poliovirus Vaccine
b. Tradename:
KINRIX
c. Manufacturer:
GlaxoSmithKline
d. Vaccine Ontology ID:
VO_0000067
e. Type:
Toxoid vaccine + Subunit vaccine + Inactivated or "killed" vaccine
f. Status:
Licensed
g. Location Licensed:
USA
h. Host Species for Licensed Use:
Human
i. Allergen:
Latex, Neomycin, Polymyxin B.
j. Preparation
The diphtheria toxin is produced by growing Corynebacterium diphtheriae in Fenton medium containing a bovine extract. After, they are detoxified with formaldehyde, concentrated by ultrafiltration, and purified by precipitation, dialysis, and sterile filtration.
k. Immunization Route
Intramuscular injection (i.m.)
l. Storage
Store refrigerated between 2° and 8°C (36° and 46°F), do not freeze.
m . Approved Age for Licensed Use
4 to 6 years of age.
n. Contraindication
A severe allergic reaction (e.g., anaphylaxis) after a previous dose of any diphtheria toxoid, tetanus toxoid, pertussis or poliovirus-containing vaccine, or to any component of KINRIX, including neomycin and polymyxin B, encephalopathy within 7 days of administration of a previous pertussis-containing vaccine and progressive neurologic disorders.
o. Description
A single dose of KINRIX is indicated for active immunization against diphtheria, tetanus, pertussis, and poliomyelitis as the fifth dose in the diphtheria, tetanus, and acellular pertussis (DTaP) vaccine series and the fourth dose in the inactivated poliovirus vaccine (IPV) series in children 4 through 6 years of age whose previous DTaP vaccine doses have been with INFANRIX and/or PEDIARIX for the first three doses and INFANRIX for the fourth dose. (FDA: KINRIX)
23. Pediacel
a. Product Name:
Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed Combined with Inactivated Poliomyelitis Vaccine and Haemophilus b Conjugate Vaccine (Tetanus Protein – Conjugate)
b. Tradename:
Pediacel
c. Manufacturer:
Sanofi Pasteur Ltd
d. Vaccine Ontology ID:
VO_0010730
e. Type:
Subunit vaccine + Inactivated or "killed" vaccine
f. Status:
Licensed
g. Location Licensed:
Canada
h. Host Species for Licensed Use:
Human
i. Adjuvant: aluminum phosphate vaccine adjuvant
j. Preservative:
2 phenoxy ethanol
k. Allergen:
Neomycin Polymyxin B Streptomycin, Latex in stopper of vial
l. Immunization Route
Intramuscular injection (i.m.)
m. Storage
Store at 2° to 8°C (35° to 46°F).
n . Approved Age for Licensed Use
2 months to 6 years of age.
o. Description
Products: Proteins, killed virus + conjugate. Other components: Bovine serum Formaldehyde, Polysorbate 80.
24. Pediarix
a. Product Name:
Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Hepatitis B (Recombinant) and Inactivated Poliovirus Vaccine Combined
b. Tradename:
Pediarix
c. Manufacturer:
GlaxoSmithKline Biologicals
d. Vaccine Ontology ID:
VO_0000082
e. CDC CVX code:
110
f. Type:
Toxoid vaccine
g. Status:
Licensed
h. Location Licensed:
United States
i. Host Species for Licensed Use:
Human
j. Adjuvant: aluminum hydroxide vaccine adjuvant
k. Allergen:
yeast, neomycin,polymyxin B
l. Preparation
The diphtheria toxin is produced by growing Corynebacterium diphtheriae in Fenton medium containing a bovine extract. The diphtheria, tetanus, and pertussis antigens are individually adsorbed onto aluminum hydroxide then diluted and combined to produce the final formulated vaccine (FDA: Pediarix).
m. Immunization Route
Intramuscular injection (i.m.)
n. Storage
The vaccine should be refrigerated between 2º and 8ºC (36º and 46ºF). Do not freeze.
o . Approved Age for Licensed Use
PEDIARIX is indicated for active immunization against diphtheria, tetanus, pertussis (whooping cough), all known subtypes of hepatitis B virus, and poliomyelitis caused by poliovirus Types 1, 2, and 3 as a three-dose primary series in infants born of HBsAg-negative mothers, beginning as early as 6 weeks of age. PEDIARIX should not be administered to any infant before the age of 6 weeks, or to individuals 7 years of age or older.
p. Contraindication
Hypersensitivity to any component of the vaccine, including yeast, neomycin, and polymyxin B, is a contraindication. The vaccine should also not be administered to anyone with a previous allergic reaction to a dose of the vaccine (FDA: Pediarix).
q. Description
It contains diphtheria and tetanus toxoids, 3 pertussis antigens (inactivated pertussis toxin [PT] and formaldehyde-treated filamentous hemagglutinin [FHA] and pertactin [69 kiloDalton outer membrane protein]), hepatitis B surface antigen, plus poliovirus Type 1 (Mahoney), Type 2 (MEF-1), and Type 3 (Saukett) (FDA: Pediarix).
25. Pentacel
a. Product Name:
Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Inactivated Poliovirus and Haemophilus b Conjugate (Tetanus Toxoid Conjugate) Vaccine
b. Tradename:
Pentacel
c. Manufacturer:
Sanofi Pasteur Limited
d. Vaccine Ontology ID:
VO_0000084
e. CDC CVX code:
120
f. Type:
Subunit vaccine + Inactivated or "killed" vaccine
g. Status:
Licensed
h. Location Licensed:
USA (License #1726), Canada
i. Host Species for Licensed Use:
Human
j. Adjuvant: aluminum phosphate vaccine adjuvant
k. Preservative:
2 phenoxy ethanol
l. Allergen:
Polymyxin B, Neomycin
m. Preparation
Corynebacterium diphtheriae is grown in modified Mueller’s growth medium. After purification by ammonium sulfate fractionation, the diphtheria toxin is detoxified with formaldehyde and diafiltered (FDA: Pentacel).
n. Immunization Route
Intramuscular injection (i.m.)
o. Storage
Store at 2° to 8°C (35° to 46°F). Do not freeze.
p . Approved Age for Licensed Use
6 weeks to 4 years of age.
q. Contraindication
A severe allergic reaction (e.g., anaphylaxis) after a previous dose of Pentacel vaccine, any ingredient of this vaccine, or any other tetanus toxoid, diphtheria toxoid, pertussis-containing vaccine, inactivated poliovirus vaccine or H influenzae type b vaccine is a contraindication (FDA: Pentacel).
r. Description
It consists of a Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed and Inactivated Poliovirus (DTaP-IPV) component and an ActHIB® vaccine component. Pentacel vaccine is indicated for active immunization against diphtheria, tetanus, pertussis, poliomyelitis and invasive disease due to Haemophilus influenzae type b (FDA: Pentacel).
26. Quadracel
a. Product Name:
Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed Combined with Inactivated Poliomyelitis Vaccine
b. Tradename:
Quadracel
c. Manufacturer:
Sanofi Pasteur Ltd
d. Vaccine Ontology ID:
VO_0010736
e. Type:
Subunit vaccine + Inactivated or "killed" vaccine
f. Status:
Licensed
g. Location Licensed:
Canada
h. Host Species for Licensed Use:
Human
i. Adjuvant: aluminum phosphate vaccine adjuvant
j. Preservative:
2 phenoxy ethanol
k. Allergen:
Polymyxin B, Neomycin
l. Immunization Route
Intramuscular injection (i.m.)
m. Storage
Store at 2 to 8C (35 to 46F). Do not freeze.
n . Approved Age for Licensed Use
2 months to six years of age.
27. rBCG-S1PT
a. Vaccine Ontology ID:
VO_0004790
b. Type:
Recombinant vector vaccine
c. Status:
Licensed
d. Host Species for Licensed Use:
Mouse
e. Antigen
BCG vaccine with S1 subunit of detoxified B. pertussis toxin; PT-9K/129G (Nascimento et al., 2008).
f. Immunization Route
Intramuscular injection (i.m.)
g. Mouse Response
  • Vaccination Protocol: Mice were immunized with 50μl of one-tenth dose of an adult mouse of DTP at day 5 (or day 12 as specified) or 105 CFU of BCG or rBCG-S1PT on day 5 according to different regimens (Nascimento et al., 2008).
  • Vaccine Immune Response Type: VO_0003057
  • Challenge Protocol: Mice were subjected to intracerebral inoculation with a lethal dose of B. pertussis with approximately 3 x 104, 3 x 105, or 9 x 105 CFU (in 30μl) on day 21 after birth.
  • Efficacy: A single dose of rBCG-S1PT at day 5 led to a 100% survival of mice, and even at an extremely high challenge dose (300 times the lethal adult dose) rBCG-S1PT still induced 50% survival of neonate-immunized mice. Mice immunized with BCG alone experienced a protective effect of 80%, however at a higher challenge dose, this effect was reduced to 50%. Mice immunized with DTP showed no protection (Nascimento et al., 2008).
28. S. gordonii-PT
a. Vaccine Ontology ID:
VO_0004670
b. Type:
Recombinant vector vaccine
c. Status:
Research
d. Host Species for Licensed Use:
Baboon
e. Preparation
(Lee et al., 1999)
f. Immunization Route
Intramuscular injection (i.m.)
29. Tripacel
a. Product Name:
Pertussis Vaccine-Acellular, Combined with Diphtheria and Tetanus Toxoids (Adsorbed)
b. Tradename:
Tripacel
c. Manufacturer:
Sanofi Pasteur Ltd
d. Vaccine Ontology ID:
VO_0010742
e. Type:
Subunit vaccine
f. Status:
Licensed
g. Location Licensed:
Canada
h. Host Species for Licensed Use:
Human
i. Adjuvant: aluminum phosphate vaccine adjuvant
j. Preservative:
2-phenoxyethanol
k. Allergen:
Latex in stopper
l. Immunization Route
Intramuscular injection (i.m.)
m. Storage
Store at at 2° to 8°C.
n . Approved Age for Licensed Use
2 months up to 8 years of age.
30. Tripedia
a. Product Name:
Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed
b. Tradename:
Tripedia
c. Manufacturer:
Sanofi Pasteur, Inc.
d. Vaccine Ontology ID:
VO_0000112
e. CDC CVX code:
20
f. Type:
Toxoid vaccine
g. Status:
Licensed
h. Location Licensed:
USA (FDA License #1725)
i. Host Species for Licensed Use:
Human
j. Adjuvant: Bordetella pertussis component vaccine adjuvant
  • VO ID: VO_0000193
  • Description: Tripedia vaccine combines diptheria and tetanus toxoids with purified pertussis antigens. It consists of 3 doses administered at intervals of 4-8 weeks (FDA: Tripedia).
k. Immunization Route
Intramuscular injection (i.m.)
l. Storage
Store between 2 and 8 degrees Celsius. DO NOT FREEZE.
m . Approved Age for Licensed Use
Tripedia vaccine is indicated for active immunization against diphtheria, tetanus, and pertussis simultaneously in infants and children 6 weeks to 7 years of age (prior to seventh birthday). Due to substantial risks of complications of the disease, completion of a primary series of pertussis vaccine early in life is strongly recommended (FDA: Tripedia).
n. Contraindication
This vaccine should not be administered to anyone with a known hypersensitivity to any component of the vaccine.
o. Description
Tripedia vaccine combines diptheria and tetanus toxoids with purified pertussis antigens. It consists of 3 doses administered at intervals of 4-8 weeks (FDA: Tripedia).
31. VC-TetC/Tcf
a. Product Name:
VC expressing B. pertussis TetC/Tcf
b. Vaccine Ontology ID:
VO_0004781
c. Type:
Recombinant vector vaccine
d. Status:
Research
e. Host Species for Licensed Use:
Baboon
f. Gene Engineering of TcfA
  • Type: Recombinant protein preparation
  • Description: An attenuated strain of Vibrio cholerae was used as a carrier for the expression of heterologous antigens such as fragment C from tetanus toxin (TetC) and tracheal colonization factor from Bordetella pertussis (Tcf) (Chen et al., 1998).
  • Detailed Gene Information: Click here.
g. Preparation
An attenuated strain of Vibrio cholerae was used as a carrier for the expression of heterologous antigens such as fragment C from tetanus toxin (TetC) and tracheal colonization factor from Bordetella pertussis (Tcf) (Chen et al., 1998).
h. Immunization Route
intranasal immunization
i. Mouse Response
  • Vaccine Immune Response Type: VO_0000287
  • Challenge Protocol: Mice were challenged with wild-type B. pertussis (Chen et al., 1998).
  • Efficacy: Mice vaccinated with IEM101 expressing Tcf experienced significant reduction in bacterial colonization of their tracheas (Chen et al., 1998).
V. References
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