|
Leishmania donovani |
Table of Contents |
- General Information
- NCBI Taxonomy ID
- Disease
- Introduction
- Microbial Pathogenesis
- Host Ranges and Animal Models
- Host Protective Immunity
- Vaccine Related Pathogen Genes
- A2
(Protective antigen)
- Beta-tubulin
(Protective antigen)
- BT1
(Protective antigen)
- cofactor-independent phosphoglycerate mutase
(Protective antigen)
- F1-ATPase
(Protective antigen)
- GRP-78
(Protective antigen)
- HASPA
(Protective antigen)
- HASPB1
(Protective antigen)
- hsp70
(Protective antigen)
- KMP-11
(Protective antigen)
- mspC
(Protective antigen)
- NH
(Protective antigen)
- NH
(Protective antigen)
- ORFF
(Protective antigen)
- P1
(Protective antigen)
- cen1
(Virmugen)
- Vaccine Related Host Genes
- Ifng (Interferon gamma)
- IgG
- Ighg1
- Ighv1-9
- Il10 (interleukin 10)
- Il2
- TNF-alpha
- Vaccine Information
- ChAd63-KH
- L. donovani Beta-tubulin Protein Vaccine
- L. donovani DNA Vaccine encoding KMP-11
- L. donovani DNA Vaccine encoding NH36 Protein
- L. donovani gp63 Protein Vaccine
- L. donovani GRP-78 Protein Vaccine
- L. donovani HASPB1 Protein Vaccine
- L. donovani Hsp70 Protein Vaccine
- L. donovani LD31 Protein Vaccine
- L. donovani ORFF Protein Vaccine
- L. donovani Recombinant LdγGCS in NIV system Vaccine
- LEISH-F1+MPL-SE vaccine
- Leishmania donovani cen1 mutant vaccine
- Leishmania vaccine using recombinant L. tarentolae strain expressing A2 antigen
- Leishmune
- pVAX-P1 DNA vaccine
- SL3261-L. donovani
- 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). |
II. Vaccine Related Pathogen Genes |
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 Gene ID :
13387967
-
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 Gene ID :
13386661
-
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 Gene ID :
13386966
-
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
|
III. Vaccine Related Host Genes |
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
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Protein Sequence : Show Sequence
>gi|7305585|ref|NP_038721.1| tumor necrosis factor [Mus musculus]
MSTESMIRDVELAEEALPQKMGGFQNSRRCLCLSLFSFLLVAGATTLFCLLNFGVIGPQRDEKFPNGLPL
ISSMAQTLTLRSSSQNSSDKPVAHVVANHQVEEQLEWLSQRANALLANGMDLKDNQLVVPADGLYLVYSQ
VLFKGQGCPDYVLLTHTVSRFAISYQEKVNLLSAVKSPCPKDTPEGAELKPWYEPIYLGGVFQLEKGDQL
SAEVNLPKYLDFAESGQVYFGVIAL
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Molecule Role :
Vaximmutor
- Related Vaccine(s):
Leishmania donovani cen1 mutant vaccine
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IV. Vaccine Information |
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1. ChAd63-KH |
a. Vaccine Ontology ID: |
VO_0003961 |
b. Type: |
Recombinant vector vaccine |
c. Status: |
Clinical trial |
d. Host Species for Licensed Use: |
Human |
e. Host Species as Laboratory Animal Model: |
mouse |
f. Antigen |
KH, a self-cleaving polyprotein comprising L. donovani HASPB and KMP-11 Proteins (Osman et al., 2017) |
g. Vector: |
adenovirus 63 |
h. Immunization Route |
Intramuscular injection (i.m.) |
i. Description |
A recombinant vector vaccine for Leishmania donovani that uses an adenovirus 63 viral vector and kH protein (Osman et al., 2017). |
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2. L. donovani Beta-tubulin Protein Vaccine |
a. Vaccine Ontology ID: |
VO_0004023 |
b. Type: |
Subunit vaccine |
c. Status: |
Research |
d. Host Species as Laboratory Animal Model: |
mouse |
e. Antigen |
four polypeptides 91(LD91), 72 (LD72), 51(LD51) and 31 (LD31)-kDa (Bhowmick and Ali, 2009) |
f. Gene Engineering of
Beta-tubulin |
- Type:
Recombinant protein preparation
- Description:
- Detailed Gene Information: Click here.
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g. Adjuvant: |
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h. Immunization Route |
Intraperitoneal injection (i.p.) |
i.
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 2.5×10^7 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).
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3. L. donovani DNA Vaccine encoding KMP-11 |
a. Vaccine Ontology ID: |
VO_0011530 |
b. Type: |
DNA vaccine |
c. Status: |
Research |
d. Host Species as Laboratory Animal Model: |
mouse |
e. Antigen |
KNP-11(Bhaumik et al., 2009) |
f. 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.
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g. Adjuvant: |
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h. Vector: |
pCMV-LIC (Bhaumik et al., 2009). |
i. Immunization Route |
Subcutaneous injection |
j.
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 × 10^6 LD second-passage promastigotes suspended in saline through intracardiac route and 2 × 10^6 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).
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4. L. donovani DNA Vaccine encoding NH36 Protein |
a. Vaccine Ontology ID: |
VO_0011542 |
b. Type: |
DNA vaccine |
c. Status: |
Research |
d. Host Species as Laboratory Animal Model: |
mouse |
e. Antigen |
NH36 (Aguilar-Be et al., 2005) |
f. Gene Engineering of
NH |
- Type:
DNA vaccine construction
- Description:
- Detailed Gene Information: Click here.
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g. Vector: |
VR1012 (Aguilar-Be et al., 2005) |
h. Immunization Route |
Intramuscular injection (i.m.) |
i.
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 × 10^8 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).
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5. L. donovani gp63 Protein Vaccine |
a. Vaccine Ontology ID: |
VO_0011532 |
b. Type: |
Subunit vaccine |
c. Status: |
Research |
d. Host Species as Laboratory Animal Model: |
mouse |
e. Antigen |
gp63 |
f. Gene Engineering of
mspC |
- Type:
Recombinant protein preparation
- Description:
- Detailed Gene Information: Click here.
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g. Adjuvant: |
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h. Immunization Route |
Intraperitoneal injection (i.p.) |
i.
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 × 10^7 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).
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6. L. donovani GRP-78 Protein Vaccine |
a. Vaccine Ontology ID: |
VO_0004022 |
b. Type: |
Subunit vaccine |
c. Status: |
Research |
d. Host Species as Laboratory Animal Model: |
mouse |
e. Antigen |
GRP-78 (Nagill and Kaur, 2010) |
f. Gene Engineering of
GRP-78 |
- Type:
Recombinant protein preparation
- Description:
- Detailed Gene Information: Click here.
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g. Adjuvant: |
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h. Immunization Route |
Subcutaneous injection |
i.
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 × 10^7 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)
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7. L. donovani HASPB1 Protein Vaccine |
a. Vaccine Ontology ID: |
VO_0004067 |
b. Type: |
Subunit vaccine |
c. Status: |
Research |
d. Host Species as Laboratory Animal Model: |
mouse |
e. Antigen |
Recombinant hydrophilic acylated surface protein B1 (HASPB1) (Stäger et al., 2000). |
f. Gene Engineering of
HASPB1 |
- Type:
Recombinant protein preparation
- Description:
- Detailed Gene Information: Click here.
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g. Adjuvant: |
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h. Immunization Route |
Subcutaneous injection |
i.
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 10^7 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).
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8. L. donovani Hsp70 Protein Vaccine |
a. Vaccine Ontology ID: |
VO_0004033 |
b. Type: |
Subunit vaccine |
c. Status: |
Research |
d. Host Species as Laboratory Animal Model: |
mouse |
e. Antigen |
LD72 (Hsp70) protein |
f. Gene Engineering of
hsp70 |
- Type:
Recombinant protein preparation
- Description:
- Detailed Gene Information: Click here.
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g. Vector: |
Liposomes |
h. Immunization Route |
Intraperitoneal injection (i.p.) |
i.
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 2.5×10^7 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).
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9. 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.
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e. Adjuvant: |
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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 2.5×10^7 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).
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10. 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.
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e. Adjuvant: |
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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 × 10^8 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).
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11. 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: |
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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 × 10^7 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).
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12. 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: |
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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).
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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).
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13. 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 |
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f. Immunization Route |
Intravenous injection (i.v.) |
g.
Hamster Response |
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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.
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14. Leishmania vaccine using recombinant L. tarentolae strain expressing A2 antigen |
a. Vaccine Ontology ID: |
VO_0004180 |
b. Type: |
Recombinant vector vaccine |
c. Status: |
Research |
d. Antigen |
mouse |
e. Gene Engineering of
A2 |
- Type:
Recombinant protein preparation
- Description:
- Detailed Gene Information: Click here.
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f. Vector: |
Leishmania tarentolae, a non-pathogenic member of the genus Leishmania (Mizbani et al., 2009). |
g. Immunization Route |
Intraperitoneal injection (i.p.) |
h.
Mouse Response |
- Host Strain:
BALB/c
- Vaccination Protocol:
In the case of i.p. immunization, total number of 5 × 10^6 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 10^7 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).
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15. 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: |
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h. Immunization Route |
Intramuscular injection (i.m.) |
i. Description |
Native fucose-mannose-ligand antigen complex(Borja-Cabrera et al., 2002) |
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16. 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.
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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 × 10^7 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).
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17. 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. Host Species as Laboratory Animal Model: |
mouse |
f. 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.
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g. 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). |
h. Immunization Route |
Intramuscular injection (i.m.) |
i.
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 2×10^6 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).
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V. References |
1. Aguilar-Be et al., 2005: Aguilar-Be I, da Silva Zardo R, Paraguai de Souza E, Borja-Cabrera GP, Rosado-Vallado M, Mut-Martin M, García-Miss Mdel R, Palatnik de Sousa CB, Dumonteil E. Cross-protective efficacy of a prophylactic Leishmania donovani DNA vaccine against visceral and cutaneous murine leishmaniasis. Infection and immunity. 2005; 73(2); 812-819. [PubMed: 15664920].
2. Arora et al., 2011: Arora SK, Masih S, Vasishta RK. Efficacy of Leishmania donovani ribosomal P1 gene as DNA vaccine in experimental visceral leishmaniasis. Experimental parasitology. 2011; ; . [PubMed: 21640106].
3. Bhaumik et al., 2009: Bhaumik S, Basu R, Sen S, Naskar K, Roy S. KMP-11 DNA immunization significantly protects against L. donovani infection but requires exogenous IL-12 as an adjuvant for comparable protection against L. major. Vaccine. 2009; 27(9); 1306-1316. [PubMed: 19162111].
4. Bhowmick and Ali, 2009: Bhowmick S, Ali N. Identification of novel Leishmania donovani antigens that help define correlates of vaccine-mediated protection in visceral leishmaniasis. PloS one. 2009; 4(6); e5820. [PubMed: 19503834].
5. Bhowmick et al., 2008: Bhowmick S, Ravindran R, Ali N. gp63 in stable cationic liposomes confers sustained vaccine immunity to susceptible BALB/c mice infected with Leishmania donovani. Infection and immunity. 2008; 76(3); 1003-1015. [PubMed: 18195029].
6. Borja-Cabrera et al., 2002: Borja-Cabrera GP, Correia Pontes NN, da Silva VO, Paraguai de Souza E, Santos WR, Gomes EM, Luz KG, Palatnik M, Palatnik de Sousa CB. Long lasting protection against canine kala-azar using the FML-QuilA saponin vaccine in an endemic area of Brazil (São Gonçalo do Amarante, RN). Vaccine. 2002; 20(27-28); 3277-3284. [PubMed: 12213397].
7. Chakravarty et al., 2011: Chakravarty J, Kumar S, Trivedi S, Rai VK, Singh A, Ashman JA, Laughlin EM, Coler RN, Kahn SJ, Beckmann AM, Cowgill KD, Reed SG, Sundar S, Piazza FM. A clinical trial to evaluate the safety and immunogenicity of the LEISH-F1+MPL-SE vaccine for use in the prevention of visceral leishmaniasis. Vaccine. 2011; 29(19); 3531-3537. [PubMed: 21414377].
8. Henriquez et al., 2010: Henriquez FL, Campbell SA, Roberts CW, Mullen AB, Burchmore R, Carter KC. Vaccination with recombinant Leishmania donovani gamma-glutamylcysteine synthetase fusion protein protects against L. donovani infection. The Journal of parasitology. 2010; 96(5); 929-936. [PubMed: 20950100].
9. Kumar et al., 2017: Kumar M, Ranjan K, Singh V, Pathak C, Pappachan A, Singh DD. Hydrophilic Acylated Surface Protein A (HASPA) of Leishmania donovani: Expression, Purification and Biophysico-Chemical Characterization. The protein journal. 2017; 36(4); 343-351. [PubMed: 28634775].
10. McAtee et al., 2017: McAtee CP, Seid CA, Hammond M, Hudspeth E, Keegan BP, Liu Z, Wei J, Zhan B, Arjona-Sabido R, Cruz-Chan V, Dumonteil E, Hotez PJ, Bottazzi ME. Expression, purification, immunogenicity and protective efficacy of a recombinant nucleoside hydrolase from Leishmania donovani, a vaccine candidate for preventing cutaneous leishmaniasis. Protein expression and purification. 2017; 130; 129-136. [PubMed: 27773761].
11. Merck Manual: Leishmaniasis: Leishmaniasis [http://www.merck.com/mmpe/sec14/ch186/ch186f.html]
12. Mizbani et al., 2009: Mizbani A, Taheri T, Zahedifard F, Taslimi Y, Azizi H, Azadmanesh K, Papadopoulou B, Rafati S. Recombinant Leishmania tarentolae expressing the A2 virulence gene as a novel candidate vaccine against visceral leishmaniasis. Vaccine. 2009; 28(1); 53-62. [PubMed: 19818721].
13. Nagill and Kaur, 2010: Nagill R, Kaur S. Enhanced efficacy and immunogenicity of 78kDa antigen formulated in various adjuvants against murine visceral leishmaniasis. Vaccine. 2010; 28(23); 4002-4012. [PubMed: 20093205].
14. Osman et al., 2017: Osman M, Mistry A, Keding A, Gabe R, Cook E, Forrester S, Wiggins R, Di Marco S, Colloca S, Siani L, Cortese R, Smith DF, Aebischer T, Kaye PM, Lacey CJ. A third generation vaccine for human visceral leishmaniasis and post kala azar dermal leishmaniasis: First-in-human trial of ChAd63-KH. PLoS neglected tropical diseases. 2017; 11(5); e0005527. [PubMed: 28498840].
15. Schroeder et al., 2011: Schroeder J, Brown N, Kaye P, Aebischer T. Single dose novel Salmonella vaccine enhances resistance against visceralizing L. major and L. donovani infection in susceptible BALB/c mice. PLoS neglected tropical diseases. 2011; 5(12); e1406. [PubMed: 22216363].
16. Selvapandiyan et al., 2009: Selvapandiyan A, Dey R, Nylen S, Duncan R, Sacks D, Nakhasi HL. Intracellular replication-deficient Leishmania donovani induces long lasting protective immunity against visceral leishmaniasis. Journal of immunology (Baltimore, Md. : 1950). 2009; 183(3); 1813-1820. [PubMed: 19592661].
17. Singh et al., 2018: Singh MK, Jamal F, Dubey AK, Shivam P, Kumari S, Pushpanjali, Ahmed G, Dikhit MR, Narayan S, Das VNR, Pandey K, Sinha KK, Das P, Singh SK. Co-factor-independent phosphoglycerate mutase of Leishmania donovani modulates macrophage signalling and promotes T-cell repertoires bearing epitopes for both MHC-I and MHC-II. Parasitology. 2018; 145(3); 292-306. [PubMed: 29140228].
18. Stäger et al., 2000: Stäger S, Smith DF, Kaye PM. Immunization with a recombinant stage-regulated surface protein from Leishmania donovani induces protection against visceral leishmaniasis. Journal of immunology (Baltimore, Md. : 1950). 2000; 165(12); 7064-7071. [PubMed: 11120835].
19. Sukumaran and Madhubala, 2004: Sukumaran B, Madhubala R. Leishmaniasis: current status of vaccine development. Current molecular medicine. 2004; 4(6); 667-679. [PubMed: 15357215].
20. Tewary et al., 2006: Tewary P, Saxena S, Madhubala R. Co-administration of IL-12 DNA with rORFF antigen confers long-term protective immunity against experimental visceral leishmaniaisis. Vaccine. 2006; 24(13); 2409-2416. [PubMed: 16413950].
21. WD: Leishmania donovani: Leishmania donovani [http://www.wrongdiagnosis.com/medical/leishmania_donovani.htm]
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