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Leishmania donovani

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. A2 (Protective antigen)
    2. Beta-tubulin (Protective antigen)
    3. BT1 (Protective antigen)
    4. cofactor-independent phosphoglycerate mutase (Protective antigen)
    5. F1-ATPase (Protective antigen)
    6. GRP-78 (Protective antigen)
    7. HASPA (Protective antigen)
    8. HASPB1 (Protective antigen)
    9. hsp70 (Protective antigen)
    10. KMP-11 (Protective antigen)
    11. mspC (Protective antigen)
    12. NH (Protective antigen)
    13. NH (Protective antigen)
    14. ORFF (Protective antigen)
    15. P1 (Protective antigen)
    16. cen1 (Virmugen)
  3. Vaccine Related Host Genes
    1. Ifng (Interferon gamma)
    2. IgG
    3. Ighg1
    4. Ighv1-9
    5. Il10 (interleukin 10)
    6. Il2
    7. TNF-alpha
  4. Vaccine Information
    1. L. donovani Beta-tubulin Protein Vaccine
    2. L. donovani DNA Vaccine encoding KMP-11
    3. L. donovani DNA Vaccine encoding NH36 Protein
    4. L. donovani gp63 Protein Vaccine
    5. L. donovani GRP-78 Protein Vaccine
    6. L. donovani HASPB1 Protein Vaccine
    7. L. donovani Hsp70 Protein Vaccine
    8. L. donovani LD31 Protein Vaccine
    9. L. donovani ORFF Protein Vaccine
    10. L. donovani Recombinant LdγGCS in NIV system Vaccine
    11. LEISH-F1+MPL-SE vaccine
    12. Leishmania donovani cen1 mutant vaccine
    13. Leishmania vaccine using recombinant L. tarentolae strain expressing A2 antigen
    14. Leishmune
    15. pVAX-P1 DNA vaccine
    16. SL3261-L. donovani
  5. References
I. General Information
1. NCBI Taxonomy ID:
5661
2. Disease:
Visceral leishmaniasis
3. Introduction
Leishmania donovani is a species that is the causal agent of visceral leishmaniasis in Mediterranean and adjacent countries, the south central section of western Asia, eastern India, northern China, Kenya, Ethiopia, and the Sudan; also found in Brazil, Argentina, Colombia, and Venezuela; in the Old World, it is transmitted by various species of Phlebotomus; New World vectors are species of Lutzomyia; dogs and other carnivores are known as reservoir hosts in some areas (WD: Leishmania donovani).
4. Microbial Pathogenesis
The intracellular amastigote form multiplies in macrophages and produces a reticuloendothelial hyperplasia grossly affecting the spleen and liver, with other lymphoid tissues being involved as well, resulting in severe hepatosplenomegaly, which usually is fatal if untreated (WD: Leishmania donovani).
5. Host Ranges and Animal Models
Vector sand flies are infected by biting infected humans or animals. Animal reservoirs vary with the Leishmania sp and location and include canines, rodents, and other animals. In the Indian subcontinent, humans are the reservoir for L. donovani (Merck Manual: Leishmaniasis).
6. Host Protective Immunity
A Strong Th1 response of cell mediated immunity is necessary for protection against L. donovani (Mizbani et al., 2009).
1. A2
  • Gene Name : A2
  • Sequence Strain (Species/Organism) : Leishmania donovani
  • VO ID : VO_0011153
  • NCBI Protein GI : 30385439
  • Taxonomy ID : 5671
  • Gene Strand (Orientation) : ?
  • Protein Name : stage-specific S antigen-like protein
  • Protein pI : 4.19
  • Protein Weight : 9285.64
  • Protein Length : 194
  • Protein Note : zymodeme MON-29
  • Protein Sequence : Show Sequence
    >AAP21105.1 stage-specific S antigen-like protein [Leishmania infantum]
    MKIRSVRPLVVLLVCVAAVLALSASAEPHKAAVDAGPLSVDVGPLSVDVGPLSVGPQSVGPLSVGPQSVD
    PLSVDVGPLSVGPQSVGPLSVDVGPLSVGPQSVGPLSVGLQAVDVSPVS
    
    
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Study results show that a single intraperitoneal administration of the A2-recombinant L. tarentolae strain expressing the Leishmania donovani A2 antigen protects BALB/c mice against L. infantum challenge and that protective immunity is associated with high levels of IFN-gamma production prior and after challenge (Mizbani et al., 2009).
  • Related Vaccine(s): Leishmania vaccine using recombinant L. tarentolae strain expressing A2 antigen
2. Beta-tubulin
  • Gene Name : Beta-tubulin
  • Sequence Strain (Species/Organism) : Leishmania donovani
  • VO ID : VO_0011155
  • NCBI Protein GI : 262233287
  • Other Database IDs : CDD:276956
    CDD:240228
  • Taxonomy ID : 5661
  • Gene Strand (Orientation) : ?
  • Protein Name : beta tubulin
  • Protein pI : 6.31
  • Protein Weight : 37694.97
  • Protein Length : 416
  • Protein Note : The beta-tubulin family; cd02187
  • Protein Sequence : Show Sequence
    >ACY38664.1 beta tubulin, partial [Leishmania donovani]
    ESAGGRYVPRAVLMDLEPGTMDSVRAGPYGQLFRPDNFIFGQSGAGNNWAKGHYTEGAELIDSVLDVCRK
    EAESCDCLQGFQLSHSLGGGTGSGMGTLLISKLREEYPDRIMMTFSVIPSPRVSDTVVEPYNTTLSVHQL
    VENSDESMCIDNEALYDICFRTLKLTTPTFGDLNHLVAAVMSGVTCCLRFPGQLNSDLRKLAVNLVPFPR
    LHFFMMGFAPLTSRGSHQYPGLSVAELTQQMFDAKNMMQAADPRHGRYLTASALFRGRMSTKEVDEQMLN
    VQNKNSSYFIEWIPNNIKSSICDIPPKGLKMSVTFIGNNTCIQEMFRRVGEQFTGMFRRKACLHWYTGEG
    MDE
    
    
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Study compared the vaccine efficacy of various L. donovani antigens encapsulated in cationic liposomes in BALB/c mice against challenge infection with L. donovani. Results demonstrated that liposomal LD51 (beta-tubulin) reduced parasite burden by 72%-75% (Bhowmick and Ali, 2009).
  • Related Vaccine(s): L. donovani Beta-tubulin Protein Vaccine
3. BT1
  • Gene Name : BT1
  • Sequence Strain (Species/Organism) : Leishmania donovani
  • VO ID : VO_0011160
  • NCBI Protein GI : 703123
  • Other Database IDs : CDD:273268
    CDD:281135
  • Taxonomy ID : 5661
  • Gene Strand (Orientation) : ?
  • Protein Name : unknown
  • Protein pI : 7.37
  • Protein Weight : 64395.53
  • Protein Length : 679
  • Protein Note : folate/biopterin transporter; TIGR00788
  • Protein Sequence : Show Sequence
    >AAA96729.1 unknown [Leishmania donovani]
    MPPAPESPPPQVAKYVHPVSARVLRAAPFLGYIPVFSIAIRSFHPKVVVAICMQRLFEKGLANGLMRLSM
    QPMLTGRYGLTGAMYQRLSTLYTLGWALNAFITVMADTFALFGYTKRWYCVVSAVGGGAFALLYGLLPAK
    ESSAKPAAAFMFLAALFMSNIDVFAVALYSERIRQRPAAGPALVSWMWGTALIGIMISSVIQGPLSDNRL
    THLGVYITAAILLLSGLLFVFNLFEERRNRAARLEDAMIEFLQNTKSASTDSTAGSLPSPHKPDGHLTID
    SRVEEEGDDDDHDEQKAAAMDAQGFVRPRMDTYLCGAVEMNRDVLLRNWRMALFCLILTLGVIANALVNI
    LGTRWDIMYVCIVVAVVVCVSSFFTLPLAIAKAVVFMYFNEILYLNLPGVLNTFYVAKPLCLPGGPHFSY
    TFYNVMNGILGSIAGIGGTMVFTHLFPHHSYRFVMGLSAVLLPAASMFDLLILKRWNLVIGIPDHAMYIL
    GDAIIYEVCDMLLNMPMMMLMCRIAPRGSESMVFALLASIYHLGTSTSSAIGYLLMETIWPVVTQGTCDY
    SNAPWLVITGHIVAPVFILPLAYVLLPSARISDHIDHTGRKVMEAALPETRTEAAEEPIATTMKRDS
    
    
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Immunization of mice with recombinant BT1 proteins (a biopterin transporter) from multigenic LD1 locus on chromosome 35 of L. donovani conferred partial protection against challenge with Leishmania donovani in a BALB/c mice (Sukumaran and Madhubala, 2004).
4. cen1
  • Gene Name : cen1
  • NCBI Protein GI : 15488542
  • Other Database IDs : CDD:185503
    CDD:28933
  • Taxonomy ID : 5661
  • Gene Strand (Orientation) : ?
  • Protein Name : centrin
  • Protein Length : 149
  • Protein Note : centrin; Provisional
  • Protein Sequence : Show Sequence
    >gi|15488542|gb|AAL01153.1|AF406767_1 centrin [Leishmania donovani]
    MAALTDEQIREAFNLFDADGSGAIDAEEMALAMKGLGFGDLSRDEVERIIRSMHTDSNGLVAYGEFEAMV
    KSRMAQKDSPEEILKAFQLFDLDKKGKISFANLKEVAKLLGENPGDDVLKEMIAEADEDGDGEVSFEEFK
    SVMLHMRGK
  • Molecule Role : Virmugen
  • Molecule Role Annotation : A cen1 mutant is attenuated in mice and hamsters and induces significant protection from challenge with wild type L. donovani (Selvapandiyan et al., 2009).
  • Related Vaccine(s): Leishmania donovani cen1 mutant vaccine
5. cofactor-independent phosphoglycerate mutase
  • Gene Name : cofactor-independent phosphoglycerate mutase
  • Sequence Strain (Species/Organism) : Leishmania donovani
  • NCBI Protein GI : ADG96010
  • Other Database IDs : CDD:215295
    CDD:293734
  • Taxonomy ID : 5661
  • Protein Name : cofactor-independent phosphoglycerate mutase
  • Protein pI : 5.52
  • Protein Weight : 56341.08
  • Protein Length : 650
  • Protein Note : 2,3-bisphosphoglycerate-independent phosphoglycerate mutase
  • Protein Sequence : Show Sequence
    >ADG96010.1 cofactor-independent phosphoglycerate mutase, partial [Leishmania donovani]
    MSALLLKLHKDLPRRKLLIVVMDGLGIGPEDDYDAVHMASTPFMDAQRQNSRHFRSVRAHGAAVGLPTDA
    DMGNSEVGHNALGAGRVVLQGASLVDDALKSGEIFTGEGYRYLLGAFSKEDSTLHLIGLLSDGGVHSRDN
    QIYSIIERAAKDGAKRIRVHVLYDGRDVPDGSSFRFTEELEAVLAKLRQNGCDAAVASGGGRMFVTMDRY
    EADWSIVERGWKAQVLGDARHFRSAKEAITTFREEDPKVTDQYYPPFVVVDEQDKPLGTIEDGDAVLCVN
    FRGDRVIEMTRAFEDEDFAKFDRVRVPKVRYAGMMRYDGDLGIPNNFLVPPPKLTRVSEEYLCGSGLKIF
    ACSETQKFGHVTYFWNGNRSGKIDDEHETFKEVPSDRVHFNKQPKMKSAEITEAAIEALKSGMYDVVRIN
    FPNGDMVGHTGDLKATIVGVQAVDESLAKLKDAVDNVNGVFIVTADHGNSDDMAQRDKKGKPIKDGKGNV
    LPLTSHTLSPVPVFIGGAGLDPRVKMRTDMPTAGLANVTATFINLLGFEAPEDYEPSLIYVEK
    
    
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : (Singh et al., 2018)
6. F1-ATPase
  • Gene Name : F1-ATPase
  • Sequence Strain (Species/Organism) : Leishmania donovani
  • VO ID : VO_0011154
  • NCBI Protein GI : 722242
  • Other Database IDs : CDD:304359
    CDD:238540
    CDD:278722
  • Taxonomy ID : 5661
  • Gene Strand (Orientation) : ?
  • Protein Name : F1-ATPase beta subunit
  • Protein pI : 4.18
  • Protein Weight : 20953.9
  • Protein Length : 292
  • Protein Note : promastigotes of Leishmania donovani Sudan 1S maintained in liquid culture as a suspension
  • Protein Sequence : Show Sequence
    >AAA73465.1 F1-ATPase beta subunit, partial (mitochondrion) [Leishmania donovani]
    KVALVYGQMNEPPGARAGVAESAVTMAEYFRDVEGQNVLLFIDNIFRFTQANSEVSALLGRIPAAVGYQP
    TLAEDLGMLQERITSTTKGSITSVQAVYVPADDITDPAPATTFSHLDATTVLDRAVAESGIYPAVNPLEC
    ASRIMDPDVIDVDHYNVAQDIVQMLTKYKELQDIIAVLGIDELSEEDKVVVDRARKVTRFLSQPFQ
    
    
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Study compared the vaccine efficacy of various L. donovani antigens encapsulated in cationic liposomes in BALB/c mice against challenge infection with L. donovani. Results demonstrated that liposomal LD31 (ATP synthase alpha chain) reduced parasite burden by 74%-77% (Bhowmick and Ali, 2009).
  • Related Vaccine(s): L. donovani LD31 Protein Vaccine
7. GRP-78
  • Gene Name : GRP-78
  • Sequence Strain (Species/Organism) : Leishmania donovani
  • VO ID : VO_0011152
  • NCBI Protein GI : 16797868
  • Other Database IDs : CDD:240227
    CDD:212681
  • Taxonomy ID : 5661
  • Gene Strand (Orientation) : ?
  • Protein Name : glucose-regulated protein 78
  • Protein pI : 4.92
  • Protein Weight : 63125.03
  • Protein Length : 710
  • Protein Note : heat shock 70 kDa protein; Provisional
  • Protein Sequence : Show Sequence
    >AAL29192.1 glucose-regulated protein 78, partial [Leishmania donovani]
    GKVEAPCVGVDLGTTYSVAGVWQKGEVHIVTNEMGNRITPSVVAFTDAERLVGDGAKNQLPQNPENTIYA
    IKRLIGRKYVDPTVQNDKKLLSYHIVADKTGKPLVQVTVKGQQKRFTPEEVSAMVLQKMKEISETFLGEK
    VKNAVVTVPAYFNDAQRQATKDSGKIAGLNVVRIINEPTAAAIAYGLNKAGEKNILVFDLGGGTFDVSLA
    DNRRGFFEVVATNGDTHLGGEDFDNNMMKFFVDGLKRKQNVDISNDQKALARLRKACEAAKRQLSSHPEA
    RVEVDSLVEGYDFSEKITRAKFEELNMALFKNTLVPVQKVLEDAKLKKSDIDEIVLVGGSTRIPKVQQLI
    KDFFSGKEPNKGINPDEAVAYGAAVQAAVLTGESEVGGKVVLVDVIPLSLGIETVGGVMTKLIERNTQIP
    TKKSQIFSTYQDNQPSVLIQVFEGERGMTKDNRLLGKFDLSGIPPAPRGVPQIEVAFDVDENSILQVTAS
    DKSSGKREEITITNDKGRLSEEEIERMVREAAEFEDEDRKVRERVEAKNSLESIAYSLRNQINDKDKLGD
    KLAADDKKAIEEAVKDALDFVDENPNADREEFEAARTKLQSVTNPIIQKVYQGTAGSGAEEADAMDDL
    
    
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : BALB/c mice were immunized with a vaccine expressing the 78kDa (GRP-78) antigen of Leishmania donovani. Challenge infection was given intracardially after 2 weeks of second booster. A significant decrease in parasite burden was seen in vaccinees over the infected controls on all post challenge days and was found that maximum protection was provided by 78kDa+rIL-12 vaccine. It was highly immunogenic as depicted by the reduction in parasite load (71-94.8%) (Nagill and Kaur, 2010).
  • Related Vaccine(s): L. donovani GRP-78 Protein Vaccine
8. HASPA
  • Gene Name : HASPA
  • Sequence Strain (Species/Organism) : Leishmania donovani
  • NCBI Protein GI : 3724130
  • Other Database IDs : UniProtKB/TrEMBL: O77299
  • Taxonomy ID : 5661
  • Gene Strand (Orientation) : ?
  • Protein Name : HASPA protein
  • Protein pI : 4.31
  • Protein Weight : 8980.51
  • Protein Length : 131
  • Protein Sequence : Show Sequence
    >CAA09787.1 HASPA protein [Leishmania donovani]
    MGSSCTKDSAKESQKRADNIDTTTRSDEKDGIHVQESAGPVQENFGDAQEKNEDGHNVGDGANGNEDGND
    NQPKEHAAGN
    
    
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : (Kumar et al., 2017)
9. HASPB1
  • Gene Name : HASPB1
  • Sequence Strain (Species/Organism) : Leishmania donovani
  • VO ID : VO_0011162
  • NCBI Protein GI : 51847753
  • Other Database IDs : CDD:273344
  • Taxonomy ID : 5661
  • Gene Strand (Orientation) : ?
  • Protein Name : cell surface protein B1
  • Protein pI : 4.46
  • Protein Weight : 15792.04
  • Protein Length : 217
  • Protein Note : K+-dependent Na+/Ca+ exchanger; TIGR00927
  • Protein Sequence : Show Sequence
    >AAU10514.1 cell surface protein B1, partial [Leishmania donovani]
    PKEDGHTQKNDGDGPKEDGHTQKNDGDGPKEDGHTQKNDGDGPKEDGHTQKNDGDGPKEDGHTQKNDGDG
    PKEDGHTQKNDGDGPKEDGHTQKNDGDGPKEDGHTQKNDGDGPKEDGHTQKNDGDAPKEDGRTQRNDGDG
    PKEDGH
    
    
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Study demonstrated for the first time that a recombinant stage-specific hydrophilic surface protein of Leishmania donovani, recombinant hydrophilic acylated surface protein B1 (HASPB1), is able to confer protection against experimental challenge with L. donovani in BALB/c mice (Stäger et al., 2000).
  • Related Vaccine(s): L. donovani HASPB1 Protein Vaccine
10. hsp70
  • Gene Name : hsp70
  • Sequence Strain (Species/Organism) : Leishmania donovani
  • VO ID : VO_0011156
  • NCBI Protein GI : 281426606
  • Other Database IDs : CDD:302596
    GOA:D2EAU9
    InterPro: IPR001023
    InterPro: IPR013126
    InterPro: IPR018181
    UniProtKB/TrEMBL: D2EAU9
  • Taxonomy ID : 5661
  • Gene Strand (Orientation) : ?
  • Protein Name : heat shock protein 70
  • Protein pI : 5.03
  • Protein Weight : 47979.15
  • Protein Length : 532
  • Protein Note : Nucleotide-Binding Domain of the sugar kinase/HSP70/actin superfamily; cl17037
  • Protein Sequence : Show Sequence
    >CAZ04896.1 heat shock protein 70, partial [Leishmania donovani]
    DSQRQATKDAGTIAGLEVLRIINEPTAAAIAYGLDKGDDGKERNVLIFDLGGGTFDVTLLTIDGGIFEVK
    ATNGDTHLGGEDFDNRLVTFFTEEFKRKNKGKNLASSHRALRRLRTACERAKRTLSSATQATIEIDALFE
    NVDFQATITRARFEELCGDLFRSTIQPVERVLQDAKMDKRSVHDVVLVGGSTRIPKVQSLVSDFFGGKEL
    NKSINPDEAVAYGAAVQAFILTGGKSKQTEGLLLLDVTPLTLGIETAGGVMTALIKRNTTIPTKKSQIFS
    TYADNQPGVHIQVFEGERAMTKDCHLLGTFDLSGIPPAPRGVPQIEVTFDLDANGILNVSAEEKGTGKRN
    QITITNDKGRLSKDEIERMVNDAMKYEADDRAQRDRVEAKNGLENYAYSMKNTLGDSNVSGKLDDSDKAT
    LNKEIDVTLEWLSSNQEATKEEYEHKQKELESVCNPIMT
    
    
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Study compared the vaccine efficacy of various L. donovani antigens encapsulated in cationic liposomes in BALB/c mice against challenge infection with L. donovani. Results demonstrated that liposomal LD72 (Hsp70) reduced parasite burden by 65%-67% (Bhowmick and Ali, 2009).
  • Related Vaccine(s): L. donovani Hsp70 Protein Vaccine
11. KMP-11
  • Gene Name : KMP-11
  • Sequence Strain (Species/Organism) : Leishmania donovani
  • VO ID : VO_0011157
  • NCBI Protein GI : 7579896
  • Other Database IDs : CDD:281087
  • Taxonomy ID : 5661
  • Gene Strand (Orientation) : ?
  • Protein Name : KMP-11
  • Protein pI : 7.09
  • Protein Weight : 11872.82
  • Protein Length : 150
  • Protein Note : Kinetoplastid membrane protein 11; pfam03037
  • Protein Sequence : Show Sequence
    >AAB33127.2 KMP-11 (kinetoplast) [Leishmania donovani]
    MATTYEEFSAKLDRLDQEFNRKMQEQNAKFFADKPDESTLSPEMREHYEKFERMIKEHTEKFNKKMHEHS
    EHFKQKFAELLEQQKAAQYPSK
    
    
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : KMP-11 DNA vaccination alone in an experimental BALB/c mice model showed significant potential in terms of resolution of splenic and hepatic parasite burden against virulent LD challenge. KMP-11 DNA immunization significantly protects against L. donovani infection (Bhaumik et al., 2009).
  • Related Vaccine(s): L. donovani DNA Vaccine encoding KMP-11 , SL3261-L. donovani
12. mspC
  • Gene Name : mspC
  • Sequence Strain (Species/Organism) : Leishmania donovani
  • VO ID : VO_0011158
  • NCBI Protein GI : 21954466
  • Other Database IDs : CDD:302875
    GOA:Q8MM48
    HSSP: 1LML
    InterPro: IPR001577
    UniProtKB/TrEMBL: Q8MM48
  • Taxonomy ID : 5661
  • Gene Strand (Orientation) : ?
  • Protein Name : GP63
  • Protein pI : 6.49
  • Protein Weight : 63738.41
  • Protein Length : 691
  • Protein Note : Leishmanolysin; cl19482
  • Protein Sequence : Show Sequence
    >CAD42816.1 GP63 [Leishmania donovani]
    MSVDSSSTHRHRSVAARLVRLAAAGAAVIAAVGTAAAWAHAGAVQHRCIHDAMHPRVRQSVARHHTAPGA
    VSAVGLPYVTLDTAAAADRRPGSAPTVVRAANWGALRIAVSTEDLTDPAYHCARVGQRVNNHAGAIATCT
    ADDILTDEKRDILVKYLIPQALQLHTERLKVRQVQDKWKVTDMVDEICGDFKVPPAHITDGLSNTDFVMY
    VASVPSEEGVLAWATTCQVFSDGHPAVGVINIPAANIASRYDQLVTRVVTHEMAHALGFSGTFFTEILVV
    TQMMNIRGKDFNVSVINSSTAVAKAREQYGCGTLEYLEIEDQGGAGSAGSHIKMRNAKDELMAPAAAAGY
    YSALTMAIFQDLGFYQADFSKAEEMPWGRNAGCAFLSEKCMEQNITKWPAMFCNVSVDVVRCPTSRLMLG
    TCGIRGYSTPFSPYWQYFTNISLGGYSPFLDYCPFVIGYGDGSCNQDASLATGFFGAFNVFSDAARCIDG
    AFRPKNRTAADGYYAGLCANVRCDTATRTYSVQVCGSMDYVNCTPGLRVELSTVSSAFEEGGYITCPPYV
    EVCQANVKGAKDFAGDSDSSSSAGDAADRAAMQRWNDRMAGLATAAMVLLGMVLSLMALVVVWLLLLTCP
    WWCCKFGGLPT
    
    
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Study showed that cationic distearoyl phosphatidylcholine (DSPC) liposomes, when used as vaccine adjuvant with the immunodominant 63-kDa glycoprotein (gp63, mspC) of Leishmania donovani promastigotes, induced significant protection against progressive visceral leishmaniasis in susceptible BALB/c mice. gp63 used without adjuvant elicited partial protection but in association with liposomes exhibited marked resistance in both the livers and spleens of the mice challenged 10 days after the last vaccination (Bhowmick et al., 2008).
  • Related Vaccine(s): L. donovani gp63 Protein Vaccine
13. NH
  • Gene Name : NH
  • Sequence Strain (Species/Organism) : Leishmania donovani
  • VO ID : VO_0011161
  • NCBI Protein GI : 19697561
  • Other Database IDs : CDD:239117
  • Taxonomy ID : 5661
  • Gene Strand (Orientation) : ?
  • Protein Name : nucleoside hydrolase
  • Protein pI : 6.51
  • Protein Weight : 30583.64
  • Protein Length : 375
  • Protein Note : nuc_hydro_IU_UC_XIUA: inosine-uridine preferring, xanthosine-inosine-uridine-adenosine-preferring and, uridine-cytidine preferring nucleoside hydrolases. Nucleoside hydrolases cleave the N-glycosidic bond in nucleosides generating ribose and the...; cd02651
  • Protein Sequence : Show Sequence
    >AAG02281.1 nucleoside hydrolase [Leishmania donovani]
    MPRKIILDCDPGIDDAVAIFLAHGNPEVELLAITTVVGNQTLEKVTRNARLVADVAGIVGVPVAAGCTKP
    LVRGVRNASQIHGETGMGNVSYPPEFKTKLDGRHAVQLIIDLIMSHEPKTITLVPTGGLTNIAMAVRLEP
    RIVDRVKEVVLMGGGYHTGNASPVAEFNVFVDPEAAHIVFNESWNVTMVGLDLTHQALATPAVQKRVKEV
    GTKPAAFMLQILDFYTKVYEKERNTYATVHDPCAVAYVIDPTVMTTEQVPVDIELNGALTTGMTVADFRY
    PRPKHCHTQVAVKLDFDKFWCLVIDALKRIGDPQ
    
    
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Experimental infection of immunized BALB/c mice demonstrated that the VR1012-NH36 DNA vaccine derived from the nucleoside hydrolase gene (NH) of L. donovani induced an 88% reduction in L. chagasi parasite load and a 65% reduction in L. mexicana lesion size (Aguilar-Be et al., 2005).
  • Related Vaccine(s): L. donovani DNA Vaccine encoding NH36 Protein
14. NH
  • Gene Name : NH
  • Sequence Strain (Species/Organism) : Leishmania donovani
  • NCBI Protein GI : AAG02281
  • Other Database IDs : CDD:239117
  • Taxonomy ID : 5661
  • Protein Name : nucleoside hydrolase
  • Protein pI : 6.51
  • Protein Weight : 30583.64
  • Protein Length : 375
  • Protein Note : nuc_hydro_IU_UC_XIUA: inosine-uridine preferring, xanthosine-inosine-uridine-adenosine-preferring and, uridine-cytidine preferring nucleoside hydrolases. Nucleoside hydrolases cleave the N-glycosidic bond in nucleosides generating ribose and the...; cd02651
  • Protein Sequence : Show Sequence
    >AAG02281.1 nucleoside hydrolase [Leishmania donovani]
    MPRKIILDCDPGIDDAVAIFLAHGNPEVELLAITTVVGNQTLEKVTRNARLVADVAGIVGVPVAAGCTKP
    LVRGVRNASQIHGETGMGNVSYPPEFKTKLDGRHAVQLIIDLIMSHEPKTITLVPTGGLTNIAMAVRLEP
    RIVDRVKEVVLMGGGYHTGNASPVAEFNVFVDPEAAHIVFNESWNVTMVGLDLTHQALATPAVQKRVKEV
    GTKPAAFMLQILDFYTKVYEKERNTYATVHDPCAVAYVIDPTVMTTEQVPVDIELNGALTTGMTVADFRY
    PRPKHCHTQVAVKLDFDKFWCLVIDALKRIGDPQ
    
    
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : (McAtee et al., 2017)
15. ORFF
  • Gene Name : ORFF
  • Sequence Strain (Species/Organism) : Leishmania donovani
  • VO ID : VO_0011159
  • NCBI Protein GI : 703122
  • Taxonomy ID : 5661
  • Gene Strand (Orientation) : ?
  • Protein Name : unknown
  • Protein pI : 5.32
  • Protein Weight : 29594.74
  • Protein Length : 334
  • Protein Sequence : Show Sequence
    >AAA96728.1 unknown [Leishmania donovani]
    MQSDARELNPGRADFWEHFYGQEDGRLQQKELHHRKAREIVERGSLMNHYEWFMQYPMYEAALKACLRAV
    PTVLSKDGATRILHTGCGNSDFCDHVEGLLSDLNPAPSSSSRTCEVLNVDICENIVTHLALHFPSRLYAV
    GDCCDLHVSSSPSMPFSSNAAWYSRDTALRLRTVLQSSVDVVFDKGTADALLSSFAGVCNPNMEAYVGEA
    LKVLRPGGLLFLISINSEDVLSPYVLSAGDGLKSFQLAYADVIELCAQDLRHLRVETLGSRYSCYGYAVV
    ASAVAE
    
    
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : An expression plasmid encoding both p35 and p40 subunits of IL-12 when co-administered with a recombinant open-reading frame (rORFF) gene from the LD1 locus of Leishmania donovani induces significant protection with around 82% protection in both liver and spleen of BALB/c mice when challenged with L. donovani (Tewary et al., 2006).
  • Related Vaccine(s): L. donovani ORFF Protein Vaccine
16. P1
  • Gene Name : P1
  • NCBI Nucleotide GI : 27465165
  • NCBI Protein GI : 27465166
  • Protein Accession : AAN60108.1
  • Other Database IDs : CDD:100109
  • Taxonomy ID : 5661
  • Gene Strand (Orientation) : ?
  • Protein Name : ribosomal protein P1-like protein
  • Protein pI : 4.09
  • Protein Weight : 11317.016
  • Protein Length : 182
  • Protein Note : Ribosomal protein P1. This subfamily represents the eukaryotic large ribosomal protein P1. Eukaryotic P1 and P2 are functionally equivalent to the bacterial protein L7/L12, but are not homologous to L7/L12. P1 is located in the L12 stalk, with proteins...; cd05831
  • DNA Sequence : Show Sequence
    >gi|27465165|gb|AY161269.1| Leishmania donovani ribosomal protein P1-like protein mRNA, complete cds
    AATTCGTGTACTTTATTAGCACGTCATCACAGAGAACACCTTCCTTACGCACTGTCCATCATCGCCATGT
    CCGCTGAGACCCTCGCGTGCACGTACGCCGCGCTCATGCTGAGTGACGCCGGCCTGCCCACCTCGGCCGA
    GAACATCGCCGCGGCGGTGAAGGCGGCCGGCGTCGAGATGCGCCCCACCCTGCCCATCATCTTTGCCCGC
    TTCCTGGAGAAGAAGTCCGTGGAGACGCTGATGGCGGCCGCCGCCGCGCAGGCCCCGACGGCCGCGTNCG
    CCCCGTCTCCGGCGGCGGGCGCCGCCTCCGCTGCANCGGNCGGCGGCAAGGTGGAGGACAAGAAGAAGGA
    CGAGCCTGAGGAAGAGGGCGACGACGACATGGGTTTTGGTCTGTTCGACTGAGCGCCCCGCATGATGACC
    GGCATATGCGAGCACATGGTTGTTTGGCCTCATGTTCTGCAACACCCGAGCATGCCGTGAGCGCTGCCTC
    TCTGCGTGCACATATATATATATGTGTGTGTGTGTGTGTGCGTGTGTTTCGCTGCTCTCTTTTTCTTTTC
    GATTTTATTTACGTGTGCGTTACTCCTTCCTCCTGCGAAAAAAAAAAAAAAAAAAAA
  • Protein Sequence : Show Sequence
    >AAN60108.1 ribosomal protein P1-like protein [Leishmania donovani]
    MSAETLACTYAALMLSDAGLPTSAENIAAAVKAAGVEMRPTLPIIFARFLEKKSVETLMAAAAAQAPTAA
    XAPSPAAGAASAAXXGGKVEDKKKDEPEEEGDDDMGFGLFD
    
    
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : DNA vaccine pVAX-P1 in a prime-boost mode was able to induce protection with reduced mortality, a significant (75.68%) decrease in splenic parasite burden and increased expression of Th1 type cytokines in immunized hamsters (Arora et al., 2011).
  • Related Vaccine(s): pVAX-P1 DNA vaccine
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): Leishmania donovani cen1 mutant vaccine
2. 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): Leishmania donovani cen1 mutant vaccine
3. Ighg1
4. Ighv1-9
  • Gene Name : Ighv1-9
  • Sequence Strain (Species/Organism) : Mus musculus
  • NCBI Gene ID : 668478
  • Genbank Accession : AC073561
  • Taxonomy ID : 10090
  • Chromosome No : 12
  • Gene Starting Position : 114583568
  • Gene Ending Position : 114583861
  • Protein Name : immunoglobulin heavy variable V1-9
  • Protein Note : Also known as Igg2a; Gm16697
  • DNA Sequence : Show Sequence
    >gi|372099098:114583568-114583861 Mus musculus strain C57BL/6J chromosome 12, GRCm38 C57BL/6J
    GTCTTGCACAGTAATAGATGGCAGAGTCCTCAGTTGTCAGGCTGCTGAGTTGCATGTAGGCTGTGTTGGA
    GGATGTATCTGCAGTGAATGTGGCCTTGCCCTTGAACTTCTCATTGTAGTTAGTACTACCACTTCCAGGT
    AAAATCTCTCCAATCCACTCAAGGCCATGTCCAGGCCTCTGCTTTACCCACTCTATCCAGTAGCCAGTGA
    ATGTGTAGCCAGTAGCCTTGCAGGAAAGCTTCACTGAGGCCCCAGGCTTCATCAGCTCAGCTCCAGACTG
    CTGCAGCTGAACCT
  • Molecule Role : Vaximmutor
  • Related Vaccine(s): Leishmania donovani cen1 mutant vaccine
5. Il10 (interleukin 10)
  • Gene Name : Il10 (interleukin 10)
  • Sequence Strain (Species/Organism) : Mus musculus
  • NCBI Gene ID : 16153
  • NCBI Protein GI : 6754318
  • Locus Tag : AL513351.1
  • Genbank Accession : NM_010548
  • Protein Accession : NM_010548
  • Other Database IDs : MGI:96537; Ensembl:ENSMUSG00000016529;
  • Taxonomy ID : 10090
  • Gene Strand (Orientation) : ?
  • DNA Sequence : Show Sequence
    >gi|6754317|ref|NM_010548.1| Mus musculus interleukin 10 (Il10), mRNA
    GGGGGGGGGGATTTAGAGACTTGCTCTTGCACTACCAAAGCCACAAAGCAGCCTTGCAGAAAAGAGAGCT
    CCATCATGCCTGGCTCAGCACTGCTATGCTGCCTGCTCTTACTGACTGGCATGAGGATCAGCAGGGGCCA
    GTACAGCCGGGAAGACAATAACTGCACCCACTTCCCAGTCGGCCAGAGCCACATGCTCCTAGAGCTGCGG
    ACTGCCTTCAGCCAGGTGAAGACTTTCTTTCAAACAAAGGACCAGCTGGACAACATACTGCTAACCGACT
    CCTTAATGCAGGACTTTAAGGGTTACTTGGGTTGCCAAGCCTTATCGGAAATGATCCAGTTTTACCTGGT
    AGAAGTGATGCCCCAGGCAGAGAAGCATGGCCCAGAAATCAAGGAGCATTTGAATTCCCTGGGTGAGAAG
    CTGAAGACCCTCAGGATGCGGCTGAGGCGCTGTCATCGATTTCTCCCCTGTGAAAATAAGAGCAAGGCAG
    TGGAGCAGGTGAAGAGTGATTTTAATAAGCTCCAAGACCAAGGTGTCTACAAGGCCATGAATGAATTTGA
    CATCTTCATCAACTGCATAGAAGCATACATGATGATCAAAATGAAAAGCTAAAACACCTGCAGTGTGTAT
    TGAGTCTGCTGGACTCCAGGACCTAGACAGAGCTCTCTAAATCTGATCCAGGGATCTTAGCTAACGGAAA
    CAACTCCTTGGAAAACCTCGTTTGTACCTCTCTCCGAAATATTTATTACCTCTGATACCTCAGTTCCCAT
    TCTATTTATTCACTGAGCTTCTCTGTGAACTATTTAGAAAGAAGCCCAATATTATAATTTTACAGTATTT
    ATTATTTTTAACCTGTGTTTAAGCTGTTTCCATTGGGGACACTTTATAGTATTTAAAGGGAGATTATATT
    ATATGATGGGAGGGGTTCTTCCTTGGGAAGCAATTGAAGCTTCTATTCTAAGGCTGGCCACACTTGAGAG
    CTGCAGGGCCCTTTGCTATGGTGTCCTTTCAATTGCTCTCATCCCTGAGTTCAGAGCTCCTAAGAGAGTT
    GTGAAGAAACTCATGGGTCTTGGGAAGAGAAACCAGGGAGATCCTTTGATGATCATTCCTGCAGCAGCTC
    AGAGGGTTCCCCTACTGTCATCCCCCAGCCGCTTCATCCCTGAAAACTGTGGCCAGTTTGTTATTTATAA
    CCACCTAAAATTAGTTCTAATAGAACTCATTTTTAACTAGAAGTAATGCAATTCCTCTGGGAATGGTGTA
    TTGTTTGTCTGCCTTTGTAGCAGCATCTAATTTTGAATAAATGGATCTTATTCG
  • Protein Sequence : Show Sequence
    >gi|6754318|ref|NP_034678.1| interleukin 10 [Mus musculus]
    MPGSALLCCLLLLTGMRISRGQYSREDNNCTHFPVGQSHMLLELRTAFSQVKTFFQTKDQLDNILLTDSL
    MQDFKGYLGCQALSEMIQFYLVEVMPQAEKHGPEIKEHLNSLGEKLKTLRMRLRRCHRFLPCENKSKAVE
    QVKSDFNKLQDQGVYKAMNEFDIFINCIEAYMMIKMKS
  • Molecule Role Annotation : IL-10 plays an important role in Th2 type immune response.
  • Related Vaccine(s): Leishmania donovani cen1 mutant vaccine
6. Il2
  • Gene Name : Il2
  • Sequence Strain (Species/Organism) : Mus musculus
  • NCBI Gene ID : 16183
  • NCBI Protein GI : 7110653
  • Locus Tag : DN-144H19.3
  • Genbank Accession : AF195954
  • Protein Accession : NP_032392
  • Taxonomy ID : 10090
  • Chromosome No : 3
  • Gene Starting Position : 37120712
  • Gene Ending Position : 37125953
  • Gene Strand (Orientation) : -
  • Protein Name : interleukin 2
  • Protein pI : 4.63
  • Protein Weight : 18506.61
  • Protein Length : 169
  • Protein Note : Also known as Il-2
  • DNA Sequence : Show Sequence
    >gi|372099107:37120712-37125953 Mus musculus strain C57BL/6J chromosome 3, GRCm38 C57BL/6J
    ATTTTTTTTTAGAGGAGAGCTTTATTTCTTGAAAACACTGATTAACATAGAGTTCACAGGAATAACTGAG
    AAGTTATTTTAGCGCTTACTTTGTGCTGTCCTAAAAATGACAGACATCTGAGCTTATTTATATTTGAATC
    ATCTAAATACTTTTATTAATGAGTCTACCTACACATGATATTTAACAATTCAATATAATAAATAATTTCA
    GATAAATAGTTTAAAACATTTTTGAGCCCTTGGGGCTTACAAAAAGAATCTTTAAAGATCCATATTTATC
    ATCTGAAGACTAGTAGTTACAAAAGATAGTAAACAATACATCCAAAAATAAATTAAAGTTAAATATTTAA
    ATAAATAGAGAGCCTTATGTGTTGTAAGCAGGAGGTACATAGTTATTGAGGGCTTGTTGAGATGATGCTT
    TGACAGAAGGCTATCCATCTCCTCAGAAAGTCCACCACAGTTGCTGACTCATCATCGAATTGGCACTCAA
    ATGTGTTGTCAGAGCCCTAAAAAAGAATATAAAATTGTAGGCTAAGGTAGCTTACTTTGCATATAATTAT
    TCTTCACGGAAGCTTTTAGGCATTTATTTTAACACTGGTTAAATATATTGAACATTCACATTTCTGAAAT
    GATCACAATTATTGGGTTATGTTTTATTATGATATCAAATGGTAAAGCATAAAAAATAAAGCTCTCCAGA
    GTTGATTACCAACGAGCATTTGATGGGAACACTGAACACTTCTGTAGAATTCAGTTGCTTGACCACTTTT
    TCTCTGGTAAGTGTACACAGCTATGCATCAATTTAGGCTTCAGGAATGGAGAAATGATACTTGTTATATG
    TTCTTTGCTAAATCTTAAGAGTCTATTATTCAATTCTTTCCCCCCCAAGTCAGAATGGGAACAACCCAGA
    GTAGGTTAGGACAAGCATCTATTGGGGGAAATTTGGAGAATTTTGTTATAGATATACCTACCCTGATACC
    AGTGTAGATGAATCACAAAGTTTGTACATGTATAAATATTATAAATTTGTTCTGTGGATTAGCTTTTTGA
    AAGCTAACCCTCTTTGCTAAAGGAGATATTTTAATTCTGTTTTTAGGTGACAAGCTGAGAAGGAAATATT
    TTGACAAATTTATGGGATGGCTTTTCCAAATCTGACTAATTCCTTGTAAGTCAAATGAGGCAGATTATTC
    CTTTTAAATAAATACTCCTTTTCAAATAAGCTGCTGTGGTCTTATATACCCTCTTTACATAGCTACTTCA
    ATATTCTAATGTCTTGAATTTTTCATTTTTAAAAATATGTGGCCCTTGAAACATTTTTCTAGTTCTCATG
    TAGCTCTAAAGTTTGTACCATTCATTAGGGGTGAACTTTCTGATGTTGGCCATAGATTTTAGAGCATCCA
    TCTTTGCATACGTAAGTACTCGATTTTAGAGCATCCATCTTAGCATACGTAAGTACTCACACCTTTCAAC
    GTCTAGATGATGTGTATTTCAGCCTGCTTTAAAAACCTCAAATGGAAGCTGGGCAGTGGTGGTGCAGGCC
    TTTAATCCCAGCACTTGGGAGGCAGAGGCAGGCGGATTTCTGAGTTCGAGGCCAGCCTGGTCTACAGAGT
    GAGTTCCAGGACAGCCAGGGCTACACAGAGAAATCCTGTCTCAAAAAAACAAACAAACAAACAAACAAGA
    AACAAACAAACAAAAAAAACAAAAACAAACAAAACAAAACCTCAAATGGAAACAGTGCACTGAAATGTGA
    CTTTGGTTTGGAAAGGACTAGCCCACACCCTCTTGGAGGCTTGCTGCTACTGTCTCACCAGAGTCCATGA
    TTCTTGTGCATTTAAAAACAAAGCTCTGCAGTGGGCTCTCCCCGTCCTGCTCTGTCCATTTTAATGGCTG
    CCATTTTTGGAGAGAAATGTCTGTTTTTCTACCAATACCAGCACAACTTCTCTGGAAAAACTTTTCAGAT
    AATTTTTTCTGATCTGATGAATGTAACACCAGCAAGAGTTGCTTGTTTCTTGTGGAATTCTACTCCGTGC
    TTTCTCTCACATCCAGTTCTATGCTGGTGTGGAGGGAGCAGAGTGTTCATGTTCCCAGTTTCCTTGCAGG
    TGATGGTAGGTGGAAATTCTAGCATCATCCTACAGTGGAAGGATTCACTTGCACAGTGACTTTAAACTTT
    GGCTGACTAAATGCACAGAACCCATCAAAGACCAGAAATGGCAAGCCACTTAAAAATGCATTTCTTCTCT
    ATTTTATTTCCAGATTAGCAAATAAAGCAACACCTTACCTTTAGTTTTACAACAGTTACTCTGATATTGC
    TGATGAAATTCTCAGCATCTTCCAATTGAAAGCTTTTGCTTTGAGTCAAATCCAGAACATGCCGCAGAGG
    TCCAAGTTCATCTTCTAGGCACTGAAGATCTTTCAATTCTGTGGCCTAGAGGAGTAATAAGCTTAACCAT
    CAGCTCAGCTCACCACATACTGAAGAGCCAGAAAGTTAGTCTGCAGTCTCTCTAATCAAGAGAAGGCAGC
    ACATAGCTTTTACCACTCCCTGTCCTCTGTAAAGGGGGACTGAGGTAATCGATGCCATAAATCTAGAAGA
    GCAAGAGCTCACAACCATAAGGGTCACCTTGACTGTTAGGCCACTCTAGTGAGCTCTTCTGGCTTCATTA
    GACTTTGTAAAAAGTCTGTGTTTCTCTACCAATGCATAGCACAAGTTCAGACTATTGTTCCAATCTACAA
    AGAAATCTGCAAGGTTCACATTCTAATATCTAATCGCAGAGTTGAGAATCACAGAAGGGTAAGGGACAGG
    AATCCTTGGATGCCAACTGTCATAGGCCTAAATCTTACAGATTAGGTTATCATGGCCCTGACTGAGGGGT
    GTCAAGATAGCCAGGAAGACACATGTAATATTTTTTAAATTTATACTTCTCTGCAATTACTAAAGATGAG
    TTTTTTAAAAACCCATATGTCAAGCTAGGAAGATGGCTTTTAAGGTAAAGGTACCTGCCACCAAACTTGA
    TGATTTGAGTTCAATTGCAGTGACCCACCCACATTGTGGAAAGAATGGCCCAACTTTCATATTTCGTCTT
    CTGACCTCCACAGTTACACTGTGATACACATGCACCTCCACACATACATACATACATACATACATACATA
    CATACATACATACATACATACATACATAAAATGTAAAATCTATTTGTCCCAATGAAAAAAGTCATAACAT
    TTTGGCAGAACACTTGGGAGAATTTTTCTGATCCATGTATGAAATAATGTTTAAATACATCATGCATACT
    TACATACATATACAGGGAAAAAGGATATTGTCTAGCTCTATAGTACACTATGATTTCCATAAAGTCAGCT
    GCTTTAAGTCTACAGTGAACTGTGTTATCTCCATTTTACCAAGTCTCACAATCAGTGTCTTTCCCACAAC
    CACATGAACGGGGAGCAAGGGTGGCCCGGTCGGTCGGTCGCTCCTTTCATTAACCACAGCCTTTGAATTA
    CATGCTTCTATTGTTTTTAAAATCTTACATACCGAATGCAGGTTAAATGAAAACATCAGCAGAATTTACC
    ACATTACTCTTGTTTTCAATAATTATTTTAAAACTTAGATTTCTAGGAATTTCACCACTCTCTAAATTAA
    CATGATCTCTGTTGTTTCTCTAACAATCCTTAGAGGAAGAGGTTTGACAAGATAACACGTAGTTCCTGAT
    TGGTCTGCTATTGACCTTCCAACTTGTTATGGTGTGTCTTGGGTATTCAGTGTGGAGCTCCTTCCCTCAC
    AGAACTCTCCAGTTTGTTACTGTGGGAGCTGAACATTATGTGACTGTAATTAAGCTGGAAGAGCAACTGG
    GGCCTTTCTTTTTCATCTCCTGTAGAACAGCTAGAGGCAAAGTTCCCCTGACTCAATAGGAATGGGTCAA
    CAGCTGCCTCTTTGTCCCCTTAGATCCCATTTTGCTCTAGGCTTGGATTTACTTGGGACAAGCTCTTTCT
    AGGACCAAAGTTATCCATTCTCTTTTGACTTTCGGGACTAGAGCAAATTTCTACCCTTGCTGGAGTTCTA
    AGAGCTTGTGTAAGCTGTTTTGTATCACACAACATTCTGCCTCCAAAGGAGACCAAAAAACCTTTCAATA
    TTGAGAGATAGTATCATGTAGTAATATTACAGCTCTCTAGTTCCACTAGTTAAAAGAGACTGTATAAATC
    CAAAATTGTTTTATACATCTCGGACTTCTTCTCTAGCACTAATAGTGTGTTTATGTGCTGTTGGCCAGAC
    ACTGTTCTGAAACCTGACAAGTGATAAGCATAGCAATGATCATTTATGTAAGTGGGTGAATGAGCATAGA
    CAACTTCCTGAGGCCATGAGAGCTAGGCCCTAGCAGGGCTGGACTCCACTGCAGATCATTGGCCCTAGAA
    TCTTAACATTGGTTATGCTGCTCCTCAAAAATGCAGTCATAGGAATCATTCTTAAAACAGTAAAGTGTGT
    GTAAAATGAGACCCTCTCAAGTCAATTTTTACATTTAAGAAGCTGAAATAATGCACCTCTCTCAAATATC
    TGTAGGACAAGCATAAAACAGAAATCAACAGTCTTTAAATTATCCCAGCATCAAAATGCAATCATCTTGC
    ATTTTCTTCTCATTCCCTTTCCCAACACATAAATACACAGGAAAAATGTAAAGAAAACCATTTAAAAGAA
    GTACCATTGTCAAGATTTTTTTACAGAGAGATATCAGAGAAACTTATTTTCTTCAGATGAGGTACTATTC
    ATCTGGTCACATGTTATTTACACGTTATACACATGTATGTTACTTTGAATTCATTAGAGCACCAGTTAAA
    CACAGAAACTCACTCACCTGCTTGGGCAAGTAAAATTTGAAGGTGAGCATCCTGGGGAGTTTCAGGTTCC
    TGTAATTCTGAGAAAGCGTAACACATTATTATTAAAGGTTATTAAACACAGCCTTTGGCAAGAAAGCTAA
    AGGTATTGCCTATAGATGGGATGGCTGTGCACTTACCTCCATCCTGCTCAGGAGCTCCTGTAGGTCCATC
    AACAGCTGCTCCAGGTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGTGCTTCCGCTGTAGAGC
    TTGAAGTGGAGCTTGAAGTGGGTGCGCTGTTGACAAGGAGCACAAGTGTCAATGTGACACAGGATGCGAG
    CTGCATGCTGTACATGCCTGCAGGACTTGAGGTCACTGTGAGGAGTGATTAGCAAGGGTGAT
  • Protein Sequence : Show Sequence
    >gi|7110653|ref|NP_032392.1| interleukin-2 precursor [Mus musculus]
    MYSMQLASCVTLTLVLLVNSAPTSSSTSSSTAEAQQQQQQQQQQQQHLEQLLMDLQELLSRMENYRNLKL
    PRMLTFKFYLPKQATELKDLQCLEDELGPLRHVLDLTQSKSFQLEDAENFISNIRVTVVKLKGSDNTFEC
    QFDDESATVVDFLRRWIAFCQSIISTSPQ
  • Molecule Role : Vaximmutor
  • Related Vaccine(s): Leishmania donovani cen1 mutant vaccine
7. TNF-alpha
  • Gene Name : TNF-alpha
  • Sequence Strain (Species/Organism) : Mus musculus
  • NCBI Gene ID : 21926
  • NCBI Protein GI : 7305585
  • Genbank Accession : AB039224
  • Protein Accession : NP_038721
  • Taxonomy ID : 10090
  • Chromosome No : 17
  • Gene Starting Position : 35199389
  • Gene Ending Position : 35201995
  • Gene Strand (Orientation) : -
  • Protein Name : tumor necrosis factor
  • Protein pI : 4.75
  • Protein Weight : 24010.47
  • Protein Length : 235
  • Protein Note : Also known as DIF; Tnfa; TNFSF2; Tnfsf1a; TNFalpha; TNF-alpha; MGC151434
  • DNA Sequence : Show Sequence
    >gi|372099093:35199389-35201995 Mus musculus strain C57BL/6J chromosome 17, GRCm38 C57BL/6J
    CTTTATTTCTCTCAATGACCCGTAGGGCGATTACAGTCACGGCTCCCGTGGGGAGCAGAGGTTCAGTGAT
    GTAGCGACAGCCTGGTCACCAAATCAGCGTTATTAAGACAATTGGGTTAGATAAATATTTTGTTTTAAAC
    ATAAGCAAAAGAGGAGGCAACAAGGTAGAGAGGCCAGGTGGGGACAGCTCAGCTCCGTTTTCACAGAAAA
    CATGTCTGTCTGAAGACAGCTTCCCACACTGGGTCCTCCAGGACACCCCGGCCTTCCAAATAAATACATT
    CATAAGCAAATAAATAAATAATAAATAAATAATAAATAATAAGTGCAAATATAAATAGAGGGGGGCTGGC
    TCTGTGAGGAAGGCTGTGCATTGCACCTCAGGGAAGAATCTGGAAAGGTCTGAAGGTAGGAAGGCCTGAG
    ATCTTATCCAGCCTCATTCTGAGACAGAGGCAACCTGACCACTCTCCCTTTGCAGAACTCAGGAATGGAC
    ATTCGAGGCTCCAGTGAATTCGGAAAGCCCATTTGAGTCCTTGATGGTGGTGCATGAGAGGCCCACAGTC
    CAGGTCACTGTCCCAGCATCTTGTGTTTCTGAGTAGTTGTTGAAAGCTCTGAGCACAGAGTTGGACCCTG
    AGCCATAATCCCCTTTCTAAGTTAGAAGGATACAGACTGGGGGCTCTGAGGAGTAGACAATAAAGGGGTC
    AGAGTAAAGGGGTCAGAGTGGGGGCTGGGTAGAGAATGGATGAACACCCATTCCCTTCACAGAGCAATGA
    CTCCAAAGTAGACCTGCCCGGACTCCGCAAAGTCTAAGTACTTGGGCAGATTGACCTCAGCGCTGAGTTG
    GTCCCCCTTCTCCAGCTGGAAGACTCCTCCCAGGTATATGGGCTCATACCAGGGTTTGAGCTCAGCCCCC
    TCAGGGGTGTCCTTGGGGCAGGGGCTCTTGACGGCAGAGAGGAGGTTGACTTTCTCCTGGTATGAGATAG
    CAAATCGGCTGACGGTGTGGGTGAGGAGCACGTAGTCGGGGCAGCCTTGTCCCTTGAAGAGAACCTGGGA
    GTAGACAAGGTACAACCCATCGGCTGGCACCACTAGTTGGTTGTCTTTGAGATCCATGCCGTTGGCCAGG
    AGGGCGTTGGCGCGCTGGCTCAGCCACTCCAGCTGCTCCTCCACTTGGTGGTTTGCTGAGGGGGGGGGGG
    AGGATTGAGTCAGTGTCACCCTCTTAGTTCACACTCCACATCCTGAGCCTCAGCAGCTACCCACACTTCA
    CTTCCGGTTCCTGCACCCTCTGTCTTTCCACATCCCATTGGCTATGAGGTCCCGGGTGGCCCCCTGATGC
    CTTGCTTTTGAGTCACTGCTCTGACTCTCACGTGCTGTCTCTAAGAGCTCTGTCTTTTCTCAGCCTGGCT
    CGACACCCCTCAACCCGCCCCCCAAAATCATGCCCCTTCATTCTCAAGGCACATGTAAAGAAATCTTACC
    TACGACGTGGGCTACAGGCTTGTCACTCGAATTTTGAGAAGATGATCCTGGAGGGGAAGAGACAAAGGCA
    AGGATGAGCCTTTTAGGCTTCCCAGCAAGCATCTATGCACTTAGACCCCTTTCCTCCCAAACCAAAGCTT
    TAAGTTCTCCCCCCACCCCATCTCATCCCATGCCTAACTGCCCTTCCTCCATCTTAAATTAAGAGAGAGG
    TGTGGGAACACTTACTGAGTGTGAGGGTCTGGGCCATAGAACTGATGAGAGGGAGGCCATTTGGGAACTT
    CTGTGTAGGAAAAGGAGGTTAGTTAAGACAGACTCACCCCAAAGGAGAAGCCTCCCGGCTGATTGCCCCG
    CTTACAGTTCCTCTTTGCCCCACCCCACCCCCCAGCTTTGTGTTTTTCTTCTTCATTCATTCATCTGTCC
    AACCCACGGCTTCTTTCTGCGGTGCCCTCTGTGCTTGATCTCCCGTTATCTCCCCTTCATCTTCCTCCTT
    ATCTCTCATGCCTCTCTCATTTCTGTCTCTGAGTTTTATCTCTTGCTTATCCCCTCTTCCCCTGGCCACA
    TCTTTCCAGATCTCTCCACGTGTGAACACACTTGTTCGTTCATTCATCTCTCTGTGCATCCGACGAAGGA
    TGTTTAGTCAGCTGGACGCATGGGTCCGAGGTCCTGACTCTGTCCCCTCCACACTCTCCTCCACCTTGCC
    CTGCCCATTAGCCCACTTCTTTCCCTCACACTGTCCTTCTTGCCCTCCTAACCCGTTTTGCTTGTGAGCG
    AGAATAAGGGTTGCCCAGACACTCACCTCATCCCTTTGGGGACCGATCACCCCGAAGTTCAGTAGACAGA
    AGAGCGTGGTGGCCCCTGCCACAAGCAGGAATGAGAAGAGGCTGAGACATAGGCACCGCCTGGAGTTCTG
    GAAGCCCCCCATCTTTTGGGGGAGTGCCTCTTCTGCCAGTTCCACGTCGCGGATCATGCTTTCTGTGCTC
    ATGGTGTCTTTTCTGGAGGGAGATGTGGCGCCTTGGGCCAGTGAGTGAAAGGGACAGAACCTGCCTGGTT
    GGCTGCTTGCTTTTCTGGGAGCTATTTCCAAGATGTTCTGGAGTTTCTGTTCTCCCTCCTGGCTAGTCCC
    TTGCTGTCCTCGCTGAG
  • Protein Sequence : Show Sequence
    >gi|7305585|ref|NP_038721.1| tumor necrosis factor [Mus musculus]
    MSTESMIRDVELAEEALPQKMGGFQNSRRCLCLSLFSFLLVAGATTLFCLLNFGVIGPQRDEKFPNGLPL
    ISSMAQTLTLRSSSQNSSDKPVAHVVANHQVEEQLEWLSQRANALLANGMDLKDNQLVVPADGLYLVYSQ
    VLFKGQGCPDYVLLTHTVSRFAISYQEKVNLLSAVKSPCPKDTPEGAELKPWYEPIYLGGVFQLEKGDQL
    SAEVNLPKYLDFAESGQVYFGVIAL
  • Molecule Role : Vaximmutor
  • Related Vaccine(s): Leishmania donovani cen1 mutant vaccine
IV. Vaccine Information
1. L. donovani Beta-tubulin Protein Vaccine
a. Vaccine Ontology ID:
VO_0004023
b. Type:
Subunit vaccine
c. Status:
Research
d. Gene Engineering of Beta-tubulin
  • Type: Recombinant protein preparation
  • Description:
  • Detailed Gene Information: Click here.
e. Adjuvant: cationic liposomal vaccine adjuvant DDA:TDB
f. Immunization Route
Intraperitoneal injection (i.p.)
g. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: Mice were immunized by intraperitoneal injections of 2.5 µg purified proteins in PBS or incorporated in liposome in a total volume of 200 µl. Animals receiving PBS or empty liposomes served as controls. Mice were boosted two times at 2-week intervals (Bhowmick and Ali, 2009).
  • Challenge Protocol: Ten days after the final immunization the mice were challenged with 2.5×107 freshly transformed stationary-phase promastigotes in 200 µl PBS injected intravenously via the tail vein (Bhowmick and Ali, 2009).
  • Efficacy: Results demonstrated that liposomal LD51 (beta-tubulin) reduced parasite burden by 72%-75% (Bhowmick and Ali, 2009).
2. L. donovani DNA Vaccine encoding KMP-11
a. Vaccine Ontology ID:
VO_0011530
b. Type:
DNA vaccine
c. Status:
Research
d. Gene Engineering of KMP-11
  • Type: DNA vaccine construction
  • Description: KMP-11was cloned into a pCMV-LIC vector for DNA vaccine candidate in mice (Bhaumik et al., 2009).
  • Detailed Gene Information: Click here.
e. Adjuvant: IL-12 vacince adjuvant
f. Vector:
pCMV-LIC (Bhaumik et al., 2009).
g. Immunization Route
Subcutaneous injection
h. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: BALB/c mice were either immunized with KMP-11 containing pCMV-LIC mammalian expression vector (pCMV-LIC KMP-11) or with blank-vector construct not harboring KMP-11 gene (pCMV-LIC). rmIL-12 (1 μg/injection) was used as an adjuvant and injected through s.c. route. 7 and 15 days before parasite challenge with LD or LM, 100 μg of endotoxin-free plasmid DNA construct (pCMV-LIC, and pCMV-LIC KMP-11) dissolved in saline and injected i.m. in the hind leg thigh muscle was used for immunization of BALB/c mice using 28-gauge needle (Bhaumik et al., 2009).
  • Immune Response: KMP-11 DNA immunization alone effectively caused a significant increase in frequency of both IFN-γ producing CD4+ T and CD8+ T cells in mice challenged with either LM or LD (Bhaumik et al., 2009).
  • Challenge Protocol: 6-weeks-old BALB/c mice were injected with 2 × 106 LD second-passage promastigotes suspended in saline through intracardiac route and 2 × 106 LM second-passage promastigotes through subcutaneous route in the hind footpad using a 28-gauge needle (Bhaumik et al., 2009).
  • Efficacy: KMP-11 DNA vaccination alone in an experimental BALB/c mice model showed significant potential in terms of resolution of splenic and hepatic parasite burden against virulent LD challenge. KMP-11 DNA immunization significantly protects against L. donovani infection (Bhaumik et al., 2009).
3. L. donovani DNA Vaccine encoding NH36 Protein
a. Vaccine Ontology ID:
VO_0011542
b. Type:
DNA vaccine
c. Status:
Research
d. Gene Engineering of NH
  • Type: DNA vaccine construction
  • Description:
  • Detailed Gene Information: Click here.
e. Vector:
VR1012 (Aguilar-Be et al., 2005)
f. Immunization Route
Intramuscular injection (i.m.)
g. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: Mice were immunized via intramuscular with 100 μg of VR1012-NH36 plasmid DNA in 100 μl of saline solution and boosted 2 weeks later by a second injection. Control groups included the empty VR1012 vector and saline solution (Aguilar-Be et al., 2005).
  • Challenge Protocol: At 2 weeks after immunization, animals were challenged by intravenous injection of 2 × 108 amastigotes of L. chagasi (MHOM/BR/72/BH46), another group of mice were challenged 2 weeks after the last immunization with 106 stationary-phase promastigotes of L. mexicana (MNYC/BZ/62/379) by s.c. injection in the hind footpad (Aguilar-Be et al., 2005).
  • Efficacy: Experimental infection of immunized BALB/c mice demonstrated that the VR1012-NH36 DNA vaccine derived from the nucleoside hydrolase gene (NH) of L. donovani induced an 88% reduction in L. chagasi parasite load and a 65% reduction in L. mexicana lesion size (Aguilar-Be et al., 2005).
4. L. donovani gp63 Protein Vaccine
a. Vaccine Ontology ID:
VO_0011532
b. Type:
Subunit vaccine
c. Status:
Research
d. Gene Engineering of mspC
  • Type: Recombinant protein preparation
  • Description:
  • Detailed Gene Information: Click here.
e. Adjuvant: liposome-based vaccine adjuvant
f. Immunization Route
Intraperitoneal injection (i.p.)
g. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: BALB/c mice were immunized by three intraperitoneal (i.p.) injections at 2-week intervals with graded doses (0.6 to 10 μg) or 2.5 μg of gp63 free in phosphate-buffered saline (PBS) or entrapped in liposomes (200 μl). Animals receiving only PBS or empty liposomes served as controls (Bhowmick et al., 2008).
  • Challenge Protocol: At 10 days or 12 weeks postimmunization, groups of mice were either sacrificed for immunological assays or challenged intravenously with 2.5 × 107 freshly transformed L. donovani promastigotes (Bhowmick et al., 2008).
  • Efficacy: gp63 used without adjuvant elicited partial protection but in association with liposomes exhibited marked resistance in both the livers and spleens of the mice challenged 10 days after the last vaccination (Bhowmick et al., 2008).
5. L. donovani GRP-78 Protein Vaccine
a. Vaccine Ontology ID:
VO_0004022
b. Type:
Subunit vaccine
c. Status:
Research
d. Gene Engineering of GRP-78
  • Type: Recombinant protein preparation
  • Description:
  • Detailed Gene Information: Click here.
e. Adjuvant: IL-12 vacince adjuvant
f. Immunization Route
Subcutaneous injection
g. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: Ten microgram of 78 kDa antigen along with different concentrations of adjuvants was used to immunize animals. Subcutaneous route was used for immunization of mice in all the groups. Twenty-five BALB/c mice were used for each immunization group and the control group (immunized with PBS only).The animals who received only PBS as vaccine candidate served as controls. Two booster doses with the same respective vaccine combination were given to all immunized groups at an interval of 2 weeks each (Nagill and Kaur, 2010).
  • Challenge Protocol: Two weeks after last booster dose, mice of control and immunized groups were challenged with 1 × 107 promastigotes (Nagill and Kaur, 2010).
  • Efficacy: Maximum protection was conferred by 78 kDa antigen + rIL-12 vaccine (with parasite load reduction of 71–94.8% on 30–90 p.c.d.) (Nagill and Kaur, 2010)
6. L. donovani HASPB1 Protein Vaccine
a. Vaccine Ontology ID:
VO_0004067
b. Type:
Subunit vaccine
c. Status:
Research
d. Antigen
Recombinant hydrophilic acylated surface protein B1 (HASPB1) (Stäger et al., 2000).
e. Gene Engineering of HASPB1
  • Type: Recombinant protein preparation
  • Description:
  • Detailed Gene Information: Click here.
f. Adjuvant: IL-12 vacince adjuvant
g. Immunization Route
Subcutaneous injection
h. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: In the first two vaccination experiments, BALB/c mice received s.c. immunization with either 1) 10 µg rHASPB1 with 1 µg murine rIL-12; 2) 10 µg rHASPB1 in saline; 3) 10 µg SLA plus 1 µg rmIL-12; 4) 1 µg rmIL-12; and 5) saline. Three weeks later, mice were boosted with the same schedule, but the IL-12 dose was reduced to 0.5 µg. After an additional 3 wk, a final boost was given omitting IL-12. In the third vaccination experiment, mice were immunized three times at 3-wk intervals with 10 µg rHASPB1 or OVA (Sigma) (Stäger et al., 2000).
  • Challenge Protocol: All mice were challenged 3 wk after the last boost with 2 x 107 amastigotes, given i.v. in the lateral tail vein (Stäger et al., 2000).
  • Efficacy: rHASPB1 provided significant protection against challenge with L. donovani (Stäger et al., 2000).
7. L. donovani Hsp70 Protein Vaccine
a. Vaccine Ontology ID:
VO_0004033
b. Type:
Subunit vaccine
c. Status:
Research
d. Antigen
LD72 (Hsp70) protein
e. Gene Engineering of hsp70
  • Type: Recombinant protein preparation
  • Description:
  • Detailed Gene Information: Click here.
f. Vector:
Liposomes
g. Immunization Route
Intraperitoneal injection (i.p.)
h. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: Mice were immunized by intraperitoneal injections of 2.5 µg purified proteins in PBS or incorporated in liposome in a total volume of 200 µl. Animals receiving PBS or empty liposomes served as controls. Mice were boosted two times at 2-week intervals (Bhowmick and Ali, 2009).
  • Challenge Protocol: Ten days after the final immunization rest of the mice were challenged with 2.5×107 freshly transformed stationary-phase promastigotes in 200 µl PBS injected intravenously via the tail vein (Bhowmick and Ali, 2009).
  • Efficacy: Mice immunized with liposomal LD72 (Hsp70) had a reduced parasite burden of 65%-67% (Bhowmick and Ali, 2009).
8. L. donovani LD31 Protein Vaccine
a. Vaccine Ontology ID:
VO_0004179
b. Type:
Subunit vaccine
c. Status:
Research
d. Gene Engineering of F1-ATPase
  • Type: Recombinant protein preparation
  • Description:
  • Detailed Gene Information: Click here.
e. Adjuvant: cationic liposomal vaccine adjuvant DDA:TDB
f. Immunization Route
Intraperitoneal injection (i.p.)
g. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: Mice were immunized by intraperitoneal injections of 2.5 µg purified proteins in PBS or incorporated in liposome in a total volume of 200 µl. Animals receiving PBS or empty liposomes served as controls. Mice were boosted two times at 2-week intervals (Bhowmick and Ali, 2009).
  • Challenge Protocol: Ten days after the final immunization the mice were challenged with 2.5×107 freshly transformed stationary-phase promastigotes in 200 µl PBS injected intravenously via the tail vein (Bhowmick and Ali, 2009).
  • Efficacy: Liposomal LD31 (ATP synthase alpha chain) reduced parasite burden by 74%-77% (Bhowmick and Ali, 2009).
9. L. donovani ORFF Protein Vaccine
a. Vaccine Ontology ID:
VO_0011539
b. Type:
Subunit vaccine
c. Status:
Research
d. Gene Engineering of ORFF
  • Type: Recombinant protein preparation
  • Description:
  • Detailed Gene Information: Click here.
e. Adjuvant: IL-12 vacince adjuvant
  • VO ID: VO_0001147
  • Description: An expression plasmid encoding both p35 and p40 subunits of IL-12 was used as an adjuvant (Tewary et al., 2006).
f. Immunization Route
Intramuscular injection (i.m.)
g. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: Injections were given at midpoint of left thigh muscle. For the vaccination studies, cell proliferation, cytokine production and antibody response BALB/c mice were immunized intramuscularly with either alum alone diluted in phosphate buffered saline (PBS) final volume 100 or 50 μg of rORFF adsorbed on alum or 100 μg of IL-12 plasmid DNA diluted in PBS or 50 μg of rORFF adsorbed on alum in combination with IL-12 DNA. Three weeks later mice were immunized with the same schedule (Tewary et al., 2006).
  • Challenge Protocol: 1 × 108 stationary phase promastigotes of L. donovani were injected intravenously via the tail vein in 100 μl of PBS per mouse (Tewary et al., 2006).
  • Efficacy: An expression plasmid encoding both p35 and p40 subunits of IL-12 when co-administered with a recombinant open-reading frame (rORFF) gene from the LD1 locus of Leishmania donovani induces significant protection with around 82% protection in both liver and spleen of BALB/c mice when challenged with L. donovani (Tewary et al., 2006).
10. L. donovani Recombinant LdγGCS in NIV system Vaccine
a. Vaccine Ontology ID:
VO_0004241
b. Type:
Subunit vaccine
c. Status:
Research
d. Antigen
Recombinant Leishmania donovani gamma-glutamyl cysteine synthetase protein (LdγGCS) (Henriquez et al., 2010).
e. Adjuvant: non-ionic surfactant vesicles
f. Immunization Route
Intravenous injection (i.v.)
g. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: The day of infection was day 0 so that vaccination occurred pre-infection on day −28 and day −14. Animals (n  =  5/treatment) were immunized with either LPS (10 ng/ml equivalent to 5 EU/ml, 1 ng/dose), LdγGCS (2 or 50 µg, used as prepared or processed to remove endotoxin), or LdγGCS incorporated into NIV (50 µg) on days −28 and −14 (Henriquez et al., 2010).
  • Challenge Protocol: On day 0 immunized mice and a control group (n  =  4–10/treatment) were infected by intravenous injection (tail vein, no anaesthetic) with 1–2 × 107 L. donovani strain 200016 amastigotes harvested from the spleen of an infected hamster (Henriquez et al., 2010).
  • Efficacy: Incorporating LdγGCS into a NIV formulation was more effective than immunization with LdγGCS alone based on its ability to induce specific antibody pre- and post-infection. However, the vesicular formulation gave a similar level of protection as immunization with LdγGCS alone (Henriquez et al., 2010).
11. LEISH-F1+MPL-SE vaccine
a. Vaccine Ontology ID:
VO_0004266
b. Type:
Subunit vaccine
c. Status:
Clinical trial
d. Antigen
Recombinant Leishmania polyprotein LEISH-F1 (formerly known as Leish-111f) antigen. The antigen component of the vaccine includes three proteins derived from L. major and conserved across various Leishmania species, including L. donovani; L. chagasi, which causes New World VL; and L. braziliensis, which causes both CL and mucosal leishmaniasis (ML) in the New World. The three proteins are: Leishmania elongation initiation factor (LeIF), thiol-specific antioxidant (TSA), and Leishmania major stress-inducible protein 1 (LmSTI1) (Chakravarty et al., 2011).
e. Adjuvant: MPL-SE vaccine adjuvant
f. Immunization Route
subcutaneous injection
g. Human Response
  • Vaccination Protocol: The subjects in this trial were healthy male and female adults ≥18 years and <55 years of age from the village near Varanasi that had experienced an outbreak of VL approximately 15 years prior to the start of the trial. Eligible subjects were enrolled into the trial in three sequential cohorts (Fig. 1a). The vaccine consisted of LEISH-F1 antigen (5 μg in Cohort 1, 10 μg in Cohort 2, and 20 μg in Cohort 3) + MPL-SE adjuvant (25 μg), and was administered subcutaneously in the upper arm in a volume of 0.5 mL on days 0, 28, and 56. Subjects were followed through day 168 (Chakravarty et al., 2011).
  • Immune Response: There were statistically significant increases in median cytokine concentrations at day 84 compared to day 0 for all measured cytokines except IL-4 in the DAT-positives and IL-10 in both DAT-negatives and DAT-positives, although in some cases the differences were quite small (Chakravarty et al., 2011).
  • Side Effects: Malaise was the predominant solicited systemic reaction, followed by myalgia, pyrexia, and headache. All local injection-site and systemic reactions were of mild or moderate severity (Chakravarty et al., 2011).
  • Description: The LEISH-F1 + MPL-SE vaccine was safe and well-tolerated in this population of DAT-negative and DAT-positive subjects (Chakravarty et al., 2011).
h. Human Response
  • Vaccination Protocol: The subjects in this trial were healthy male and female adults ≥18 years and <55 years of age from the village near Varanasi that had experienced an outbreak of VL approximately 15 years prior to the start of the trial. Eligible subjects were enrolled into the trial in three sequential cohorts (Fig. 1a). The vaccine consisted of LEISH-F1 antigen (5 μg in Cohort 1, 10 μg in Cohort 2, and 20 μg in Cohort 3) + MPL-SE adjuvant (25 μg), and was administered subcutaneously in the upper arm in a volume of 0.5 mL on days 0, 28, and 56. Subjects were followed through day 168 (Chakravarty et al., 2011).
  • Immune Response: There were statistically significant increases in median cytokine concentrations at day 84 compared to day 0 for all measured cytokines except IL-4 in the DAT-positives and IL-10 in both DAT-negatives and DAT-positives, although in some cases the differences were quite small (Chakravarty et al., 2011).
  • Side Effects: Malaise was the predominant solicited systemic reaction, followed by myalgia, pyrexia, and headache. All local injection-site and systemic reactions were of mild or moderate severity (Chakravarty et al., 2011).
  • Description: The LEISH-F1 + MPL-SE vaccine was safe and well-tolerated in this population of DAT-negative and DAT-positive subjects (Chakravarty et al., 2011).
12. Leishmania donovani cen1 mutant vaccine
a. Vaccine Ontology ID:
VO_0003005
b. Type:
Live, attenuated vaccine
c. Status:
Research
d. Host Species as Laboratory Animal Model:
Mouse, hamster
e. Gene Engineering of cen1
f. Immunization Route
Intravenous injection (i.v.)
g. Hamster Response
h. Mouse Response
  • Persistence: A cen1 mutant is attenuated in mice (Selvapandiyan et al., 2009).
  • Efficacy: A cen1 mutant induces significant protection in mice from challenge with wild type L. donovani (Selvapandiyan et al., 2009).
  • Host Gene Response of Ifng (Interferon gamma)
    • Gene Response: The results thus indicate an increased IFN-γ secretion coinciding with reduced IL-10 production among the immunized mice. In the restimulated CD4+ T cells from the spleen, the IFN-γ/IL-10 ratio was significantly higher in the immunized mice both at the time of challenge (5 weeks after immunization) and after challenge (5 weeks after immunization plus 10 weeks after challenge) compared with either naive or naive-challenged controls. We also observed an absolute requirement for IFN-γ in LdCen1−/−-induced immunity. IFN-γ knockout mice immunized with LdCen1−/− for 5 wk followed by challenge were not protected (Selvapandiyan et al., 2009).
    • Detailed Gene Information: Click here.
  • Host Gene Response of Ighv1-9
    • Gene Response: Sera from BALB/c mice taken 10 wk post challenge after 5, 12, or 16 immunization weeks were measured for Leishmania-specific IgG2a responses. Results indicated a significantly higher level of IgG2a populations in the immune-challenged groups compared with the naive challenged groups (Selvapandiyan et al., 2009).
    • Detailed Gene Information: Click here.
  • Host Gene Response of Il2
    • Gene Response: The number of T cells producing IL-2 increased significantly as compared to naive mice 5 weeks after immunization in CD4+ and CD8+ cells as well as 5 weeks after immunization plus 10 weeks after challenge in both CD4+ and CD8+ cells (Selvapandiyan et al., 2009).
    • Detailed Gene Information: Click here.
  • Host Gene Response of TNF-alpha
    • Gene Response: The number of T cells producing TNF-alpha increased significantly as compared to naive mice 5 weeks after immunization in CD8+ cells as well as 5 weeks after immunization plus 10 weeks after challenge in both CD4+ and CD8+ cells (Selvapandiyan et al., 2009).
    • Detailed Gene Information: Click here.
13. Leishmania vaccine using recombinant L. tarentolae strain expressing A2 antigen
a. Vaccine Ontology ID:
VO_0004180
b. Type:
Subunit vaccine
c. Status:
Research
d. Gene Engineering of A2
  • Type: Recombinant protein preparation
  • Description:
  • Detailed Gene Information: Click here.
e. Vector:
Leishmania tarentolae, a non-pathogenic member of the genus Leishmania (Mizbani et al., 2009).
f. Immunization Route
Intraperitoneal injection (i.p.)
g. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: In the case of i.p. immunization, total number of 5 × 106 stationary-phase promastigotes were used. Mice were immunized with L. tarentolae expressing the GFP only as a control and another group were immunized with recombinant L. tarentolae-A2 (Mizbani et al., 2009).
  • Challenge Protocol: Six weeks after immunization, animals were challenged with 107 virulent stationary-phase L. infantum promastigotes through the lateral tail vein (Mizbani et al., 2009).
  • Efficacy: Study results show that a single intraperitoneal administration of the A2-recombinant L. tarentolae strain expressing the Leishmania donovani A2 antigen protects BALB/c mice against L. infantum challenge and that protective immunity is associated with high levels of IFN-gamma production prior and after challenge (Mizbani et al., 2009).
14. Leishmune
a. Tradename:
Leishmune
b. Manufacturer:
Fort Dodge
c. Vaccine Ontology ID:
VO_0001200
d. Type:
Inactivated or "killed" vaccine
e. Status:
Licensed
f. Host Species for Licensed Use:
Dog
g. Adjuvant: QuilA vaccine adjuvant
h. Immunization Route
Intramuscular injection (i.m.)
i. Description
Native fucose-mannose-ligand antigen complex(Borja-Cabrera et al., 2002)
15. pVAX-P1 DNA vaccine
a. Vaccine Ontology ID:
VO_0004272
b. Type:
DNA vaccine
c. Status:
Research
d. Antigen
P1 gene of Leishmania donovani (Arora et al., 2011).
e. Gene Engineering of P1
  • Type: DNA vaccine construction
  • Description: The purified full-length ORF cloned non-directionally in pGEMT-Easy vector was digested out and then directionally sub-cloned in pVAX1 vector (Invitrogen, USA). The purified plasmid DNA containing full-length ORF was confirmed by DNA sequencing also. The plasmid DNA was made endotoxin-free by using Endofree Plasmid DNA Mega Purification Kit (Qiagen, Hilden, Germany) according to the manufacturer’s instructions. The endotoxin free plasmid DNA (termed pVAX-P1) was used for the immunization of animals as DNA vaccine (Arora et al., 2011).
  • Detailed Gene Information: Click here.
f. Vector:
pVAX1 (Arora et al., 2011)
g. Immunization Route
Intramuscular injection (i.m.)
h. Description
pVAX-P1 DNA vaccine, given in prime-boost mode is protective against L. donovani (Arora et al., 2011).
i. Hamster Response
  • Host Strain: Syrian golden
  • Vaccination Protocol: Six weeks old Syrian golden hamsters (Mesocricetus auratus) were immunized in the following groups, with 6 hamsters per group. Group I: Naïve animals (Unimmunized – uninfected) were given PBS only and not challenged, group II: Animals were immunized with recombinant protein vaccine, rLdP1 (50 μg) along with Complete Freund’s adjuvant and two booster doses of same amount of antigen given with Incomplete Freund’s adjuvant, group III: Hamsters immunized with plasmid DNA vaccine alone, pVAX1-P1 single dose, group IV: Hamsters immunized with pVAX-P1 and given a prime-boost dose after 15 days, group V: Hamsters immunized with pVAX1-vector only and group VI: Unimmunized – were given PBS only (Arora et al., 2011).
  • Challenge Protocol: All the animals except group I, were challenged with 1 × 107 promastigotes (from late log-phase axenic cultures) intracardially (i.c.) on day 28. The hamsters were observed for 6–8 weeks post challenge (p.c.). At the end of 10 weeks post infection, the surviving animals were euthanized and parasitological and immunological parameters were studied (Arora et al., 2011).
  • Efficacy: Prime-boost immunization with pVAX-21 DNA vaccine resisted the increase in spleen parasite burden by 75.68% (Arora et al., 2011).
16. SL3261-L. donovani
a. Vaccine Ontology ID:
VO_0004672
b. Type:
Recombinant vector vaccine
c. Status:
Research
d. Host Species for Licensed Use:
Baboon
e. Gene Engineering of KMP-11
  • Type: Recombinant vector construction
  • Description: The sequence encoding cholera toxin B subunit signal peptide was followed by SpeI/BglII sites for in frame directional cloning of ORF of interest fused with downstream sequences coding for a hemagglutinin epitope (HA)-tag and the transporter domain of AIDA (Schroeder et al., 2011)
  • Detailed Gene Information: Click here.
f. Preparation
Five chosen antigens were differentially expressed on the surface or in the cytosol of Salmonella typhimurium SL3261. A two-step procedure was developed to select optimal Salmonella vaccine strains for each antigen, based on bacterial fitness and antigen expression levels (Schroeder et al., 2011).
g. Immunization Route
Intramuscular injection (i.m.)
h. Mouse Response
  • Vaccination Protocol: Mice were vaccinated with a single dose of Salmonella vaccine strains, the carrier control SL3261 or treated with PBS (Schroeder et al., 2011).
  • Vaccine Immune Response Type: VO_0003057
  • Challenge Protocol: Mice were subsequently challenged with 2×106 late-stationary phase L. major promastigotes into the left hind footpad (Schroeder et al., 2011).
  • Efficacy: The vaccine strains of Salmonella expressing the novel Leishmania antigens LinJ08.1190 and LinJ23.0410 significantly reduced visceralisation of L. major and enhanced systemic resistance against L. donovani in susceptible BALB/c mice. The results show that Salmonella are valid vaccine carriers for inducing resistance against visceral leishmaniasis but that their use may not be suitable for all antigens (Schroeder et al., 2011).
V. References
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