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Rickettsia spp

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. OmpA (Protective antigen)
    2. OmpB (Protective antigen)
    3. SpaP (Protective antigen)
  3. Vaccine Related Host Genes
    1. Ifng (Interferon gamma)
  4. Vaccine Information
    1. Rickettsia DNA Vaccine encoding OmpB Protein boosted with Recombinant OmpB
    2. Rickettsia rickettsii vaccine using M. vaccae expressing R. rickettsii OmpA Protein
  5. References
I. General Information
1. NCBI Taxonomy ID:
780
2. Disease:
Spotted Fever, Typhus
3. Introduction
Rickettsia is a genus of non-motile, Gram-negative, non-sporeforming, highly pleomorphic bacteria that can present as cocci (0.1 μm in diameter), rods (1–4 μm long) or thread-like (10 μm long). Obligate intracellular parasites, the Rickettsia survival depends on entry, growth, and replication within the cytoplasm of eukaryotic host cells (typically endothelial cells). Because of this, Rickettsia cannot live in artificial nutrient environments and are grown either in tissue or embryo cultures (typically, chicken embryos are used). In the past they were positioned somewhere between viruses and true bacteria. The majority of Rickettsia bacteria are susceptible to antibiotics of the tetracycline group. Rickettsia species are carried by many ticks, fleas, and lice, and cause diseases in humans such as typhus, rickettsialpox, Boutonneuse fever, African tick bite fever, Rocky Mountain spotted fever, Australian Tick Typhus, Flinders Island Spotted Fever and Queensland tick typhus. They have also been associated with a range of plant diseases. Like viruses, they only grow inside living cells. The name rickettsia is often used for any member of the Rickettsiales. They are thought to be the closest living relatives to bacteria that were the origin of the mitochondria organelle that exists inside most eukaryotic cells (Wiki: Rickettsia). Rickettsial diseases vary in clinical severity according to the virulence of the Rickettsia and host factors, such as age, male gender, alcoholism, and other underlying diseases. The most virulent rickettsiae are R. rickettsii and R. prowazekii, which kill a significant portion of infected persons, unless the diseases are treated sufficiently early in the course of infection with an effective antimicrobial agent, usually doxycycline (Textbook of Bacteriology).
4. Microbial Pathogenesis
All rickettsial infections begin with introduction of the organisms into the skin, either through a tick bite or cutaneous abrasions contaminated by flea or louse feces. Rickettsiae enter dermal cells including endothelium and proliferate locally intracellularly with endothelial cell-to-cell spread for most SFG rickettsioses resulting in an eschar or tache noire, a zone of dermal and epidermal necrosis approximately 1 cm in diameter with a surrounding zone of erythema. Eschars do not occur in epidemic and murine typhus and are rarely observed in Rocky Mountain spotted fever (Textbook of Bacteriology).
5. Host Ranges and Animal Models
Rickettsia are generally carried by ticks and fleas and can be transmitted to humans and other warm-blooded mammals (Wiki: Rickettsia).
6. Host Protective Immunity
Rickettsial infection stimulates an early innate immune response with activation of natural killer cells and production of gamma interferon (gamma IFN), which act in concert to dampen rickettsial growth. Acquired immunity develops with clonal expansion of CD4 and CD8 T lymphocytes as well as antibody-producing B cells. Clearance of intraendothelial rickettsiae is achieved by rickettsicidal effects due to cytokine activation of the infected endothelial cells themselves. Cell mediated immunity (CMI) plays an important role as expected in infection by an intracellular parasite, but antibodies (including those directed at epitopes of OmpA and OmpB) also play a role in protective immunity (Textbook of Bacteriology).
1. OmpA
  • Gene Name : OmpA
  • Sequence Strain (Species/Organism) : Rickettsia rickettsii
  • VO ID : VO_0011234
  • NCBI Protein GI : 112710
  • Other Database IDs : CDD:162346
    CDD:154874
  • Taxonomy ID : 783
  • Gene Strand (Orientation) : ?
  • Protein Name : Outer membrane protein A
  • Protein Length : 2249
  • Protein Note : rOmp A; 190 kDa antigen; Cell surface antigen; rOmpA
  • Protein Sequence : Show Sequence
    >gi|112710|sp|P15921.1|OMPA_RICRI RecName: Full=Outer membrane protein A; AltName: Full=rOmp A; Short=rOmpA; AltName: Full=190 kDa antigen; AltName: Full=Cell surface antigen; Contains: RecName: Full=120 kDa surface-exposed protein; AltName: Full=120 kDa outer membrane protein ompA; Contains: RecName: Full=32 kDa beta peptide; Flags: Precursor
    MANISPKLFKKAIQQGLKAALFTTSTAAIMLSSSGALGVATGVIATNNNAAFSNNVGNNNWNEITAAGVA
    NGTPAGGPQNNWAFTYGGDYTVTADAADRIIKAINVAGTTPVGLNITQNTVVGSIITKGNLLPVTLNAGK
    SLTLNGNNAVAANHGFDAPADNYTGLGNIALGGANAALIIQSAAPSKITLAGNIDGGGIITVKTDAAING
    TIGNTNALATVNVGAGTATLGGAVIKATTTKLTNAASVLTLTNANAVLTGAIDNTTGGDNVGVLNLNGAL
    SQVTGDIGNTNSLATISVGAGTATLGGAVIKATTTKLTDAASAVKFTNPVVVTGAIDNTGNANNGIVTFT
    GNSTVTGNVGNTNALATVNVGAGLLQVQGGVVKANTINLTDNASAVTFTNPVVVTGAIDNTGNANNGIVT
    FTGNSTVTGDIGNTNALATVNVGAGTATLGGAVIKATTTKLTNAASVLTLTNANAVLTGAIDNTTGGDNV
    GVLNLNGALSQVTGNIGNTNSLATISVGAGTATLGGAVIKATTTKLTDAASAVKFTNPVVVTGAIDNTGN
    ANNGIVTFTGNSTVTGDIGNTNSLATISVGAGTATLGGAVIKATTTKLTNAASVLTLTNANAVLTGAIDN
    TTGGDNVGVLNLNGALSQVTGDIGNTNSLATISVGAGTATLGGAVIKATTTKITNAVSAVKFTNPVVVTG
    AIDSTGNANNGIVTFTGNSTVTGDIGNTNALATVNVGAGTATLGGAVIKATTTKLTNAASVLTLTNANAV
    LTGAIDNTTGGDNVGVLNLNGALSQVTGDIGNTNSLATISVGAGTATLGGAVIKATTTKLTNAASVLTLT
    NANAVLTGAVDNTTGGDNVGVLNLNGALSQVTGDIGNTNSLATISVGAGTATLGGAVIKATTTKLTNAAS
    VLTLTNANAVLTGAIDNTTGGDNVGVLNLNGALSQVTGDIGNTNSLATISVGAGTATLGGAVIKATTTKL
    TDAASAVKFTNPVVVTGAIDNTGNANNGIVTFTGNSTVTGNVGNTNALATVNVGAGLLQVQGGVVKANTI
    NLTDNASAVTFTNPVVVTGAIDNTGNANNGIVTFTGNSTVTGNVGNTNALATVNVGAGLLQVQGGVVKAN
    TINLTDNASAVTFTNPVVVTGAIDNTGNANNGIVTFTGNSTVTGDIGNTNALATVNVGAGITLQAGGSLA
    ANNIDFGARSTLEFNGPLDGGGKAIPYYFKGAIANGNNAILNVNTKLLTASHLTIGTVAEINIGAGNLFT
    IDASVGDVTILNAQNINFRARDSVLVLSNLTGVGVNNILLAADLVAPGADEGTVVFNGGVNGLNVGSNVA
    GTARNIGDGGGNKFNTLLIYNAVTITDDVNLEGIQNVLINKNADFTSSTAFNAGAIQINDATYTIDANNG
    NLNIPAGNIQFAHADAQLVLQNSSGNDRTITLGANIDPDNDDEGIVILNSVTAGKKLTIAGGKTFGGAHK
    LQTILFKGAGDCSTAGTTFNTTNIVLDITGQLELGATTANVVLFNDAVQLTQTGNIGGFLDFNAKNGMVT
    LNNNVNVAGAVQNTGGTNNGTLIVLGASNLNRVNGIAMLKVGAGNVTIAKGGKVKIGEIQGTGTNTLTLP
    AHFNLTGSINKTGGQALKLNFMNGGSVSGVVGTAANSVGDITTAGATSFASSVNAKGTATLGGTTSFANT
    FTNTGAVTLAKGSITSFAKNVTATSFVANSATINFSNSLAFNSNITGGGTTLTLGANQVTYTGTGSFTDT
    LTLNTTFDGAAKSGGNILIKSGSTLDLSGVSTLALVVTATNFDMNNISPDTKYTVISAETAGGLKPTSKE
    NVKITINNDNRFVDFTFDASTLTLFAEDIAADVIDGDFAPGGPLANIPNAANIKKSLELMEDAPNGSDAR
    QAFNNFGLMTPLQEADATTHLIQDVVKPSDTIAAVNNQVVASNISSNITALNARMDKVQSGNKGPVSSGD
    EDMDAKFGAWISPFVGNATQKMCNSISGYKSDTTGGTIGFDGFVSDDLALGLAYTRADTDIKLKNNKTGD
    KNKVESNIYSLYGLYNVPYENLFVEAIASYSDNKIRSKSRRVIATTLETVGYQTANGKYKSESYTGQLMA
    GYTYMMPENINLTPLAGLRYSTIKDKGYKETGTTYQNLTVKGKNYNTFDGLLGAKVSSNINVNEIVLTPE
    LYAMVDYAFKNKVSAIDARLQGMTAPLPTNSFKQSKTSFDVGVGVTAKHKMMEYRINYDTNIGSKYFAQQ
    GSVKVRVNF
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Immunization with one of the constructs of M. vaccae expressing OmpA in combination with booster immunization with the homologous recombinant protein protected a significant portion of mice from lethal challenge (Crocquet-Valdes et al., 2001).
  • Related Vaccine(s): Rickettsia rickettsii vaccine using M. vaccae expressing R. rickettsii OmpA Protein
2. OmpB
  • Gene Name : OmpB
  • Sequence Strain (Species/Organism) : Rickettsia rickettsii
  • VO ID : VO_0011235
  • NCBI Protein GI : 6685726
  • Other Database IDs : CDD:152769
    CDD:162346
    CDD:154874
  • Taxonomy ID : 783
  • Gene Strand (Orientation) : ?
  • Protein Name : Outer membrane protein B
  • Protein Length : 1654
  • Protein Note : rOmp B; 168 kDa surface-layer protein; Surface protein antigen; Cell surface antigen 5; rOmpB; Sca5
  • Protein Sequence : Show Sequence
    >gi|6685726|sp|Q53047.1|OMPB_RICRI RecName: Full=Outer membrane protein B; AltName: Full=rOmp B; Short=rOmpB; AltName: Full=168 kDa surface-layer protein; AltName: Full=Surface protein antigen; AltName: Full=Cell surface antigen 5; Short=Sca5; Contains: RecName: Full=120 kDa surface-exposed protein; AltName: Full=Surface protein antigen; AltName: Full=120 kDa outer membrane protein ompB; AltName: Full=p120; Contains: RecName: Full=32 kDa beta peptide; Flags: Precursor
    MAQKPNFLKKLISAGLVTASTATIVASFAGSAMGAAIQQNRTTNGAATTVDGAGFDQTAAPANVGVALNA
    VITANANNGINFNTPAGSFNGLLLNTANNLAVTVSEDTTLGFITNVVHNAHSFNLTLNAGKTLTITGQGV
    TNAQAAATKNAQNVVVQFNNGAAIDNNDLKGVGRIDFGAPASTLVFNLANPTTQKAPLILGDNAVIANGV
    NGTLNVTNGFIQVSNKSFATVKAINIADGQGIIFNTDANNANTLNLQAGGTTINFTGTDGTGRLVLLSKH
    AAATNFNITGSLGGNLKGVIEFNTVAVDGQLTANAGAANAVIGTNNGAGRAAGFVVSVDNGKVATIDGQV
    YAKDMVIQSANATGQVNFRHIVDVGADGTTAFKTAASKVTITQDSNFGNTDFGNLAAQIKVPNAITLTGN
    FTGDASNPGNTAGVITFDANGTLESASADANVAVTNNITAIEASGAGVVQLSGTHAAELRLGNAGSIFKL
    ADGTVINGKVNQTALVGGALAAGTITLDGSATITGDIGNAGGAAALQRITLANDAKKTLTLGGANIIGAG
    GGTIDLQANGGTIKLTSTQNNIVVDFDLAIATDQTGVVDASSLTNAQTLTINGKIGTIGANNKTLGQFNI
    GSSKTVLSNGNVAINELVIGNDGAVQFAHDTYLITRTTNAAGQGKIIFNPVVNNGTTLAAGTNLGSATNP
    LAEINFGSKGVNVDTVLNVGEGVNLYATNITTTDANVGSFVFNAGGTNIVSGTVGGQQGNKFNTVALENG
    TTVKFLGNATFNGNTTIAANSTLQIGGNYTADCVASADGTGIVEFVNTGPITVTLNKQAAPVNALKQITV
    SGPGNVVINEIGNAGNHHGAVTDTIAFENSSLGAVVFLPRGIPFNDAGNTMPLTIKSTVGNKTAKGFDVP
    SVVVLGVDSVIADGQVIGDQNNIVGLGLGSDNGIIVNATTLYAGISTLNNNQGTVTLSGGVPNTPGTVYG
    LGTGIGASKFKQVTFTTDYNNLGNIIATNATINDGVTVTTGGIAGIGFDGKITLGSVNGNGNVRFADGIL
    SNSTSMIGTTKANNGTVTYLGNAFVGNIGDSDTPVASVRFTGSDSGAGLQGNIYSQVIDFGTYNLGIVNS
    NIILGGGTTAINGKIDLVTNTLTFASGTSTWGNNTSIETTLTLANGNIGHIVILEGAQVNTTTTGTTTIK
    VQDNANANFSGTQTYTLIQGGARFNGTLGSPNFAVTGSNRFVNYSLIRAANQDYVITRTNNAENVVTNDI
    ANSPFGGAPGVDQNVTTFVNATNTAAYNNLLLAKNSANSANFVGAIVTDTSAAITNVQLDLAKDIQAQLG
    NRLGALRYLGTPETAEMAGPEAGAISAAVAAGDEAIDNVAYGIWAKPFYTDAHQSKKGGLAGYKAKTTGV
    VIGLDTLANDNLMIGAAIGITKTDIKHQDYKKGDKTDVNGFSFSLYGAQQLVKNFFAQGSAIFSLNQVKN
    KSQRYFFDANGNMSKQIAAGHYDNMTFGGNLTVGYDYNAMQGVLVTPMAGLSYLKSSDENYKETGTTVAN
    KQVNSKFSDRTDLIVGAKVAGSTMNITDLAVYPEVHAFVVHKVTGRLSKTQSVLDGQVTPCINQPDRTTK
    TSYNLGLSASIRSDAKMEYGIGYDAQISSKYTAHQGTLKVRVNF
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : R. rickettsii OmpB contain B and T lymphocyte epitopes. Immunizations with each of two fragments from OmpB (rompB1550-2738 and rompB2459-4123) conferred protection against challenge with a lethal dose of R. conorii. Protection appeared to be better achieved among the groups that received both DNA and recombinant protein immunizations, although recombinant protein immunizations alone provided some protection (Díaz-Montero et al., 2001).
  • Related Vaccine(s): Rickettsia DNA Vaccine encoding OmpB Protein boosted with Recombinant OmpB
3. SpaP
  • Gene Name : SpaP
  • Sequence Strain (Species/Organism) : Rickettsia prowazekii
  • VO ID : VO_0011317
  • NCBI Protein GI : 152498
  • Other Database IDs : CDD:152769
    CDD:162346
    CDD:154874
  • Taxonomy ID : 782
  • Gene Strand (Orientation) : ?
  • Protein Name : surface antigen
  • Protein Length : 1612
  • Protein Note : Rickettsia outer membrane protein B; pfam12334
  • Protein Sequence : Show Sequence
    >gi|152498|gb|AAA26390.1| surface antigen [Rickettsia prowazekii]
    MGAAMQYNRTTNAAATTFDGIGFDQAAGANIPVAPNSVITANANNPITFNTPNGHLNSLFLDTANDLAVT
    INEDTTLGFITNIAQQAKFFNFTVAAGKILNITGQGITVQEASNTINAQNALTKVHGGAAINANDLSGLG
    SITFAVCPSVLEFNLINPINSRSSSYHLVSNSKIVNGGNGILNITNGFIQVSDNTFAGIKTINIDDCQGL
    MFNSTPDAANTLNLQAGGNTINFNGIDGTGKLVLVSKNGAATEFNVTGTLGGNLKGIIELNTAAVAGKLI
    SLGGAANAVIGTDNGAGRAAGFIVSVDNGNAATISGQVYAKNMVIQSANAGGQVTFEHIVDVGLGGTTNF
    KTADSKVIITENSNFGSTNFGNLDTQIVVPDTKILKGNFIGDVKNNGNTAGVITFNANGALVSASTDPNI
    AVTNINAIEAEGAGVVELSGIHIAELRLGNGGSIFKLADGTVINGPVNQNALMNNNALAAGSIQLDGSAI
    ITGDIGNGGVNAALQHITLANDASKILALDGANIIGANVGGAIHFQANGGTIKLTNTQNNIVVNFDLDIT
    TDKTGVVDASSLTNNQTLTINGSIGTVVANTKTLAQLNIGSSKTILNAGDVAINELVIENNGSVQLNHNT
    YLITKTINAANQGQIIVAADPLNTNTTLADGTNLGSAENPLSTIHFATKAANADSILNVGKGVNLYANNI
    TTNDANVGSLHFRSGGTSIVSGTVGGQQGHKLNNLILDNGTTVKFLGDTTFNGGTKIEGKSILQISNNYT
    TDHVESADNTGTLEFVNTDPITVTLNKQGAYFGVLKQVIISGPGNIVFNEIGNVGIVHGIAANSISFENA
    SLGTSLFLPSGTPLDVLTIKSTVGNGTVDNFNAPIVVVSGIDSMINNGQIIGDKKNIIALSLGSDNSITV
    NANTLYSGIRTTKNNQGTVTLSGGMPNNPGTIYGLGLENGSPKLKQVTFTTDYNNLGSIIANNVTINDDV
    TLTTGGIAGTDFDAKITLGSVNGNANVRFVDSTFSDPRSMIVATQANKGTVTYLGNALVSNIGSLDTPVA
    SVRFTGNDSGAGLQGNIYSQNIDFGTYNLTILNSNVILGGGTTAINGEIDLLTNNLIFANGTSTWGDNTS
    ISTTLNVSSGNIGQVVIAEDAQVNATTTGTTTIKIQDNANANFSGTQAYTLIQGGARFNGTLGAPNFAVT
    GSNIFVKYELIRDSNQDYVLTRTNDVLNVVTTAVGNSAIANAPGVSQNISRCLESTNTAAYNNMLLAKDP
    SDVATFVGAIATDTSAAVTTVNLNDTQKTQDLLSNRLGTLRYLSNAETSDVAGSATGAVSSGDEAEVSYG
    VWAKPFYNIAEQDKKGGIAGYKAKTTGVVVGLDTLASDNLMIGAAIGITKTDIKHQDYKKGDKTDINGLS
    FSLYGSQQLVKNFFAQGNSIFTLNKVKSKSQRYFFESNGKMSKQIAAGNYDNMTFGGNLIFGYDYNAMPN
    VLVTPMAGLSYLKSSNENYKETGTTVANKRINSKFSDRVDLIVGAKVAGSTVNITDIVIYPEIHSFVVHK
    VNGKLSNSQSMLDGQTAPFISQPDRTAKTSYNIGLSANIKSDAKMEYGIGYDFNSASKYTAHQGTLKVRV
    NF
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Guinea pigs immunized with different doses of the SPA appear to be protected against challenge with live organisms as compared with nonimmunized controls (Carl et al., 1990).
1. Ifng (Interferon gamma)
  • Gene Name : Ifng (Interferon gamma)
  • Sequence Strain (Species/Organism) : Mouse
  • NCBI Gene ID : 15978
  • NCBI Protein GI : 33468859
  • Genbank Accession : NM_008337
  • Protein Accession : NP_032363.1
  • Other Database IDs : MGI:107656; UniProt: P01580
  • Taxonomy ID : 10090
  • Gene Strand (Orientation) : ?
  • DNA Sequence : Show Sequence
    >gi|145966741|ref|NM_008337.3| Mus musculus interferon gamma (Ifng), mRNA
    ATAGCTGCCATCGGCTGACCTAGAGAAGACACATCAGCTGATCCTTTGGACCCTCTGACTTGAGACAGAA
    GTTCTGGGCTTCTCCTCCTGCGGCCTAGCTCTGAGACAATGAACGCTACACACTGCATCTTGGCTTTGCA
    GCTCTTCCTCATGGCTGTTTCTGGCTGTTACTGCCACGGCACAGTCATTGAAAGCCTAGAAAGTCTGAAT
    AACTATTTTAACTCAAGTGGCATAGATGTGGAAGAAAAGAGTCTCTTCTTGGATATCTGGAGGAACTGGC
    AAAAGGATGGTGACATGAAAATCCTGCAGAGCCAGATTATCTCTTTCTACCTCAGACTCTTTGAAGTCTT
    GAAAGACAATCAGGCCATCAGCAACAACATAAGCGTCATTGAATCACACCTGATTACTACCTTCTTCAGC
    AACAGCAAGGCGAAAAAGGATGCATTCATGAGTATTGCCAAGTTTGAGGTCAACAACCCACAGGTCCAGC
    GCCAAGCATTCAATGAGCTCATCCGAGTGGTCCACCAGCTGTTGCCGGAATCCAGCCTCAGGAAGCGGAA
    AAGGAGTCGCTGCTGATTCGGGGTGGGGAAGAGATTGTCCCAATAAGAATAATTCTGCCAGCACTATTTG
    AATTTTTAAATCTAAACCTATTTATTAATATTTAAAACTATTTATATGGAGAATCTATTTTAGATGCATC
    AACCAAAGAAGTATTTATAGTAACAACTTATATGTGATAAGAGTGAATTCCTATTAATATATGTGTTATT
    TATAATTTCTGTCTCCTCAACTATTTCTCTTTGACCAATTAATTATTCTTTCTGACTAATTAGCCAAGAC
    TGTGATTGCGGGGTTGTATCTGGGGGTGGGGGACAGCCAAGCGGCTGACTGAACTCAGATTGTAGCTTGT
    ACCTTTACTTCACTGACCAATAAGAAACATTCAGAGCTGCAGTGACCCCGGGAGGTGCTGCTGATGGGAG
    GAGATGTCTACACTCCGGGCCAGCGCTTTAACAGCAGGCCAGACAGCACTCGAATGTGTCAGGTAGTAAC
    AGGCTGTCCCTGAAAGAAAGCAGTGTCTCAAGAGACTTGACACCTGGTGCTTCCCTATACAGCTGAAAAC
    TGTGACTACACCCGAATGACAAATAACTCGCTCATTTATAGTTTATCACTGTCTAATTGCATATGAATAA
    AGTATACCTTTGCAACC
  • Protein Sequence : Show Sequence
    >gi|33468859|ref|NP_032363.1| interferon gamma [Mus musculus]
    MNATHCILALQLFLMAVSGCYCHGTVIESLESLNNYFNSSGIDVEEKSLFLDIWRNWQKDGDMKILQSQI
    ISFYLRLFEVLKDNQAISNNISVIESHLITTFFSNSKAKKDAFMSIAKFEVNNPQVQRQAFNELIRVVHQ
    LLPESSLRKRKRSRC
  • Molecule Role Annotation : IFN-gamma plays a critical role in Th1 type immune response. It is important for protection against infections by various viruses and intracellular bacteria.
  • Additional Molecule Role : Vaximmutor
  • Additional Molecule Role Annotation : The experimental data demonstrated that three time vaccinations with BCG in BALB/c mice induced strong TB Ag-specific IFN-gamma immune responses in splenocytes (Wang et al., 2009).
  • Related Vaccine(s): Rickettsia rickettsii vaccine using M. vaccae expressing R. rickettsii OmpA Protein
IV. Vaccine Information
1. Rickettsia DNA Vaccine encoding OmpB Protein boosted with Recombinant OmpB
a. Vaccine Ontology ID:
VO_0011389
b. Type:
DNA vaccine
c. Status:
Research
d. Gene Engineering of OmpB
  • Type: DNA vaccine construction
  • Description:
  • Detailed Gene Information: Click here.
e. Vector:
pcDNA3.1/V5-His-TOPO (Díaz-Montero et al., 2001)
f. Immunization Route
Intramuscular injection (i.m.)
g. Mouse Response
  • Host Strain: C3H/ HeN
  • Vaccination Protocol: Animals were immunized with only two doses of DNA (100 μg of recombinant plasmid and 100 μg of pIL-12) four weeks apart given intramuscularly in the tibialis anterior muscles. All mice that received DNA immunizations were also administered two booster immunizations of 100 μg each of the homologous purified recombinant protein. Control mice received either non-recombinant vector plus β-galactosidase-His recombinant protein (negative control) or a sublethal immunizing dose of R. conorii (positive
    control) (Díaz-Montero et al., 2001).
  • Challenge Protocol: Mice were challenged with 3 median lethal doses (LD50) of R. conorii. In a previous experiment, this dose was shown to kill 100% of naive mice. After challenge, animals were observed daily for morbidity and mortality (Díaz-Montero et al., 2001).
  • Efficacy: R. rickettsii OmpB contain B and T lymphocyte epitopes. Immunizations with each of two fragments from OmpB (rompB1550-2738 and rompB2459-4123) conferred protection against challenge with a lethal dose of R. conorii. Protection appeared to be better achieved among the groups that received both DNA and recombinant protein immunizations, although recombinant protein immunizations alone provided some protection (Díaz-Montero et al., 2001).
2. Rickettsia rickettsii vaccine using M. vaccae expressing R. rickettsii OmpA Protein
a. Vaccine Ontology ID:
VO_0011388
b. Type:
Recombinant vector vaccine
c. Status:
Research
d. Gene Engineering of OmpA
  • Type: Recombinant vector construction
  • Description:
  • Detailed Gene Information: Click here.
e. Adjuvant: incomplete Freunds adjuvant
f. Vector:
Mycobacterium vaccae (Crocquet-Valdes et al., 2001).
g. Immunization Route
Subcutaneous injection
h. Mouse Response
  • Host Strain: C3H/HeN mice
  • Vaccination Protocol: 6–8-week-old male C3H/HeN mice were were inoculated subcutaneously with 1×108 to 5×108 of recombinant M. vaccae transformants containing rompA3006–3960. As a negative control mice were immunized with either PBS or inoculated subcutaneously with M. vaccae/pCR7, another negative control. Booster inoculations were performed 1 month later with the same dose and route. Mice immunized with M. vaccae transformants were given two additional doses of 100 μg per mouse of recombinant rickettsial GST fusion protein OmpA755–1301 suspended in incomplete Freund’s adjuvant with a 1 month interval between the immunizations (Crocquet-Valdes et al., 2001).
  • Challenge Protocol: One month after the last inoculation, all groups of mice were challenged intravenously with three LD50 of R. conorii and observed daily for 2 weeks for morbidity and mortality (Crocquet-Valdes et al., 2001).
  • Efficacy: Immunization with one of the constructs of Mycobacterium vaccae expressing Rickettsia rickettsii OmpA in combination with booster immunization with the homologous recombinant protein protected a significant portion of mice from lethal challenge with the closely related bacterium, R. conorii, in mice (Crocquet-Valdes et al., 2001).
  • Host Gene Response of Ifng (Interferon gamma)
    • Gene Response: Production of IFN-gamma by antigen-exposed T-lymphocytes of DNA vaccine recipients indicated that cellular immunity had been stimulated. IFN-γ levels in supernatant fluid of rickettsial antigen-stimulated splenocytes from an animal that received both DNA and protein vaccinations were 47% or more higher than the controls that were vaccinated with the vector and GST or were sham-immunized with saline. This observed difference was significant and was seen in spleen cells the day before the challenge (Crocquet-Valdes et al., 2001).
    • Detailed Gene Information: Click here.
V. References
1. Carl et al., 1990: Carl M, Dobson ME, Ching WM, Dasch GA. Characterization of the gene encoding the protective paracrystalline-surface-layer protein of Rickettsia prowazekii: presence of a truncated identical homolog in Rickettsia typhi. Proceedings of the National Academy of Sciences of the United States of America. 1990; 87(21); 8237-8241. [PubMed: 2122457].
2. Crocquet-Valdes et al., 2001: Crocquet-Valdes PA, Díaz-Montero CM, Feng HM, Li H, Barrett AD, Walker DH. Immunization with a portion of rickettsial outer membrane protein A stimulates protective immunity against spotted fever rickettsiosis. Vaccine. 2001; 20(5-6); 979-988. [PubMed: 11738766].
3. Díaz-Montero et al., 2001: Díaz-Montero CM, Feng HM, Crocquet-Valdes PA, Walker DH. Identification of protective components of two major outer membrane proteins of spotted fever group Rickettsiae. The American journal of tropical medicine and hygiene. 2001; 65(4); 371-378. [PubMed: 11693887].
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