VIOLIN: Vaccine Investigation and Online Information Network

Leishmania infantum

Table of Contents

General Information
Vaccine Related Pathogen Genes
1. H1 (Protective antigen)
2. HASPB (Protective antigen)
3. HASPB1 (Protective antigen)
4. kmp-11 gene C (Protective antigen)
5. LIPO-A (Protective antigen)
6. P36/LACK (Protective antigen)
7. prohibitin (Protective antigen)
8. SMT (Protective antigen)
9. HSP70 II (Virmugen)
Vaccine Related Host Genes
1. Ighv1-9
Vaccine Information
References

I. General Information

1. NCBI Taxonomy ID:

5671

2. Disease:

Infantile visceral leishmaniasis

3. Introduction

Leishmania infantum is the causative agent of infantile visceral leishmaniasis in the Mediterranean region of the Old World and in Latin America, where it has been called Leishmania chagasi. It is also an unusual cause of cutaneous leishmaniasis. Wild canids and domestic dogs are the natural reservoir of this organism. L. infantum is closely-related to L. donovani and some authors believe that these two species are so close as to actually be subspecies of each other, however phylogenetic analyses can distinguish between these two groups (Wiki: Leishmania infantum).

4. Microbial Pathogenesis

The parasites are transmitted by the bite of sandflies and the infecting promastigotes differentiate into and replicate as amastigotes within macrophages in the mammalian host (Goto et al., 2007).

5. Host Ranges and Animal Models

Wild canids and domestic dogs are the natural reservoir of L. infantum, and the parasite is vectored by sandflies which pass on infection when they bite mammals including humans (Goto et al., 2007).

6. Host Protective Immunity

In common with other intracellular pathogens, cellular immune responses are critical for protection against leishmaniasis. Th1 immune responses play an important role in mediating protection against Leishmania, including roles for CD4+ and CD8+ T cells, IFN-γ, IL-12, TNF-α and NO, whereas inhibitory effects have been reported for IL-10 and TGF-β (Goto et al., 2007).

II. Vaccine Related Pathogen Genes

1. H1

Gene Name : H1
Sequence Strain (Species/Organism) : Leishmania infantum
VO ID : VO_0011285
NCBI Gene ID : 5070063
NCBI Nucleotide GI : 78146499
NCBI Protein GI : 78146500
Protein Accession : ABB22792.1
Taxonomy ID : 5671
Gene Strand (Orientation) : ?
Protein Name : histone H1
Protein pI : 12.41
Protein Weight : 10687.41
Protein Length : 155
Protein Note : L.infH1

DNA Sequence : Show Sequence

>gi|78146499|gb|DQ232891.1| Leishmania infantum histone H1 gene, complete cds
ATGTCCTCTGATTCCGCCGTTGCTGCCCTTTCCGCTGCCATGACCTCGCCGCAGAAGTCTCCTCGCTCGT
CGCCGAAGAAGACGGCTGCGAAGAAGGCCGCGGCGAAGAAGGCCGCGGCGAAGAAGGCCGGGGCGAAGAA
GGCCGGGGCGAAGAAGGCGGTGAGGAAGGTGGCTACGCCGAAGAAGCCGGCGAAGAAGGCTGCGAAGAAG
GCCGCGAAGAAGCCGGCGAAGAAGGTCGCGAAGAAGCCGGCGAAGAAGGCTGCGAAGAAGCCGGCGAAGA
AGCCGGCGAAGAAGGCTGCGAAGAAGGCCGCGGCGAAGAAGTAA

Protein Sequence : Show Sequence

>ABB22792.1 histone H1 [Leishmania infantum]
MSSDSAVAALSAAMTSPQKSPRSSPKKTAAKKAAAKKAAAKKAGAKKAGAKKAVRKVATPKKPAKKAAKK
AAKKPAKKVAKKPAKKAAKKPAKKPAKKAAKKAAAKK

Molecule Role : Protective antigen
Molecule Role Annotation : Following infection with L. infantum promastigotes, five out of eight beagle dogs immunized with H1 Montanide remained free of clinical signs, compared to two out of eight dogs in the control group. The results demonstrate that H1 antigens with Montanide were able to induce partial protection against canine leishmaniasis, even under extreme experimental challenge conditions (Moreno et al., 2007).
Related Vaccine(s): L. infantum H1 protein vaccine

2. HASPB

Gene Name : HASPB
Sequence Strain (Species/Organism) : Leishmania infantum
NCBI Gene ID : 5069221
NCBI Protein GI : XP_001465795
Other Database IDs : CDD:332332
UniProtKB/TrEMBL: A4I0F4
Taxonomy ID : 435258
Gene Strand (Orientation) : ?
Protein Name : hydrophilic acylated surface protein b
Protein pI : 4.53
Protein Weight : 26499.252
Protein Length : 335
Protein Note : Sodium/calcium exchanger protein; cl27511

Protein Sequence : Show Sequence

>XP_001465795.2 hydrophilic acylated surface protein b [Leishmania infantum JPCM5]
MGAYCTKDSAKEPQKRADNIHKTTEANHRGAAGVPPKHAGGAMNDSAPKEDGHTQKNDGDGPKEDGRTQK
NDDGGPKEDGHTQKNDGDGPKEDGRTQKNNGDGPKEDGHTQKNDGDAPKEDGRTQKNDGDGPKEDGRTQK
NDGDGPKEDGRTQKNDGDGPKEDGRTQKNDGDGPKEDGHTQKNDGDGPKEDGRTQKNDGGGPKEDENLQQ
NDGNAQEKNEDGHNVGDGANGNEDGNDDQPKEQVAGN

Molecule Role : Protective antigen
Molecule Role Annotation : (Mortazavidehkordi et al., 2016)

3. HASPB1

Gene Name : HASPB1
Sequence Strain (Species/Organism) : Leishmania infantum
VO ID : VO_0011286
NCBI Gene ID : 5069221
NCBI Nucleotide GI : 3724133
NCBI Protein GI : 3724134
Protein Accession : CAA09789.1
Other Database IDs : CDD:273344
UniProtKB/TrEMBL: O77301
Taxonomy ID : 5661
Gene Strand (Orientation) : ?
Protein Name : HASPB1 protein
Protein pI : 4.47
Protein Weight : 42746.61
Protein Length : 457
Protein Note : K+-dependent Na+/Ca+ exchanger; TIGR00927

DNA Sequence : Show Sequence

>gi|3724133|emb|AJ011810.1| Leishmania donovani HASPB1 gene
ATGGGAACTTCTTGTACAAAGGACTCCGCAAAGGAGCCCCAGAAGCGTGCTGATAACATCCATAAAACCA
CTGAGGCCAATCACGGAGGCGCCACTGGTGTGCCCCCGAAGCACACCGGCAGTGCGATGAACGACTCTGC
CCCGAAGGAGGACGGCCATACACAGAAAAATGACGGCGATGGCCCTAAGGAGGACGGCCATACACAGAAA
AATGACGGCGATGGCCCGAAGGAGGACGGCCATACACAGAAAAATGACGGCGATGGCCCTAAGGAGGACG
GCCATACACAGAAAAATGACGGCGATGGCCCGAAGGAGGACGGCCATACACAGAAAAATGACGGCGATGG
CCCTAAGGAGGACGGCCATACACAGAAAAATGACGGCGATGGCCCGAAGGAGGACGGCCATACACAGAAA
AATGACGGCGATGGCCCTAAGGAGGACGGCCATACACAGAAAAATGACGGCGATGGCCCGAAGGAGGACG
GCCATACACAGAAAAATGACGGCGATGGCCCTAAGGAGGACGGCCATACACAGAAAAATGACGGCGATGG
CCCGAAGGAGGACGGCCATACACAGAAAAATGACGGCGATGGCCCGAAGGAGGACGGCCATACACAGAAA
AATGACGGCGATGGCCCTAAGGAGGACGGCCATACACAGAAAAATGACGGCGATGGCCCGAAGGAGGACG
GCCATACACAGAAAAATGACGGCGATGGCCCTAAGGAGGACGGCCATACACAGAAAAATGACGGCGATGG
CCCGAAGGAGGACGGCCATACACAGAAAAATGACGGCGATGGCCCTAAGGAGGACGGCCATACACAGAAA
AATGACGGCGATGGCCCGAAGGAGGACGGCCATACACAGAAAAATGACGGCGATGGCCCTAAGGAGGACG
GCCATACACAGAAAAATGACGGCGATGGCCCGAAGGAGGACGGCCATACACAGAAAAATGACGGCGATGG
CCCTAAGGAGGACGGCCATACACAGAAAAATGACGGCGATGGCCCGAAGGAGGACGGCCATACACAGAAA
AATGACGGCGATGGCCCTAAGGAGGGTGAGAATCTGCAGCAAAACGATGGGGATGCGCAGGAGAAGAACG
AAGATGGACACAACGTGGGGGATGGAGCTAACGGCAATGAGGATGGTAACGATGATCAGCCGAAGGAGCA
CGCTGCCGGCAACTAG

Protein Sequence : Show Sequence

>CAA09789.1 HASPB1 protein [Leishmania donovani]
MGTSCTKDSAKEPQKRADNIHKTTEANHGGATGVPPKHTGSAMNDSAPKEDGHTQKNDGDGPKEDGHTQK
NDGDGPKEDGHTQKNDGDGPKEDGHTQKNDGDGPKEDGHTQKNDGDGPKEDGHTQKNDGDGPKEDGHTQK
NDGDGPKEDGHTQKNDGDGPKEDGHTQKNDGDGPKEDGHTQKNDGDGPKEDGHTQKNDGDGPKEDGHTQK
NDGDGPKEDGHTQKNDGDGPKEDGHTQKNDGDGPKEDGHTQKNDGDGPKEDGHTQKNDGDGPKEDGHTQK
NDGDGPKEDGHTQKNDGDGPKEDGHTQKNDGDGPKEDGHTQKNDGDGPKEDGHTQKNDGDGPKEDGHTQK
NDGDGPKEGENLQQNDGDAQEKNEDGHNVGDGANGNEDGNDDQPKEHAAGN

Molecule Role : Protective antigen
Molecule Role Annotation : Following infection with L. infantum promastigotes, four out of eight beagle dogs immunized with HASPB1 Montanide remained free of clinical signs, compared to two out of eight dogs in the control group. The results demonstrate that HASPB1 antigens with Montanide were able to induce partial protection against canine leishmaniasis, even under extreme experimental challenge conditions (Moreno et al., 2007).
Related Vaccine(s): L. infantum HASPB1 protein vaccine

4. HSP70 II

Gene Name : HSP70 II
Sequence Strain (Species/Organism) : Leishmania infantum JPCM5
NCBI Gene ID : 5073319
NCBI Protein GI : 146101862
Locus Tag : LINJ_35_4220
Genbank Accession : FR796467
Protein Accession : XP_001469224
Taxonomy ID : 435258
Chromosome No : 35
Gene Starting Position : 1642294
Gene Ending Position : 1644234
Gene Strand (Orientation) : ?
Protein pI : 5.06
Protein Weight : 65055.03
Protein Length : 646

DNA Sequence : Show Sequence

>gi|339899319:1642294-1644234 Leishmania infantum JPCM5 chromosome 35, complete sequence
AATGAATCGACACAACAAGTTCTACGCTGAGGTGGCTGGCGAGTTGGAGGGGGACGACTACTACGGTGAC
GACGACGACTACAACTATGATGAAGAGTACGAGGAGGAGGGGGAGTACGACGAGGCAGCGTACGAGGCCA
CAGCGAGTGCGGCGCCGCCTGAACCGGCGCACATGTCCGAAAGCACCGCTCAGGCCACTGCGTCCGCCGC
TCCGGCCGTGCGCGTTAACCCGTACACAACGATATCGCCGCAGGTGGACGATGACTACGAGCTGCTCGAC
ATGCTGTTGCCGCAGCTGCACGCCTTGTGGAAAGCAAGTGCACCGACGATGCTGCCGCTCTCGGAGGGCG
AGGCGGTCACGGCACTTCGGGCAAGCAACTACGACGTCGAGCCCGCCTTCCTGCAACTCAAAGAAAAGCG
AGACGAGGAGCGCTCCAAGCGCGGCGGCGGCGTCCTGAAGGTCACCGCAGCTGCTGGACCCGCGAACCGG
GCATCCACTTTTCCAGCTGTCGAGTCACCCGAACCCGGCGGCGAGGAGGCGAGCGATAACGAGGGCAACT
CTGCATCGCCGAGCGCGAGTTCTGGCCGCACCACGACCACCTTGAGGGGCTCGAAGGGCACATCGCAGCG
ACGCACGAAGCAGATGCTAGAGATGGAACCGGACAAGGAGAAGCCGGACTGCACGTTTGTGATTGCCGGC
CACGTCGATGCCGGAAAGAGCACCACGCTGGGCCACCTCCTCCTGCTCTTGGGCCGCGTTAGCATCCAGG
ATGTCGAGAGAAACGAAAAAGCAGACCGCACGCACCGCAAGGACTCCTTCAAGTACGCCTGGCTGCTGGA
CCAGTGTGAGGAGGAGCGGCGCCGTGGCGTCACCATCGACTCCGGCTCTTTCTGCTTCGAAACGGAGCAC
CGTCGCGTGCACATCCTCGATGCCCCAGGGCACAAGGACTTTGTGCTCAGCATGATCAGCAGTGCCACCC
AGGCCGATGCTGCCTTGCTCGTCGTGACGGCGGCCACCTCCGAGTTCGAGACGGGGCTGCACCACGGTAC
CAAGTCTCATCTTCTGGTCTTGAAAACGCTCGGCGTCGGGTCCATTGTCGTCGCCGTCAACAAGATGGAC
GCCGTCGCCTATTCACAGGAGCGCTACGACTACGTGGTGCGGGAGCTGCAGCTCCTGCTCAAGCAGACCC
GCATCCCGGAGGAAGCCATCATCGGCTTTTGCCCCATTAGTGGCATGGCAGGCGTCAACATCACTCAGCG
GGGCGCCAAGGAGACGCCTTGGTACCACGATCTCAGCTTGATCGAGATGATTGACAAGTGTCCGTTGGAG
AGTCGCCTGCTGAACAGACCGCTGCGCCTGAGTCTGCAAGACGTGCAGGGCACCACCCTCTACGCCAAGG
TCGAGAGCGGAAGGCTCTTCACAGGGGACACGGTTCATTTCGTGCCGAGCGAGGTGCGGGTCGCTGTCAA
GTCGATTCAGAAGCCCACTGTGGCTGGCCCTGTTCTCGTCGCCTTTGCTGGCGAGATGGTAGAGATCAGC
ACGAACTCGTCCGTGACAGGACTGTACCCGGGCTGTGTGGGCTGCGAGCCGAATTTGTTAATCCACAGTT
CCACCGACTTTGAGGCGCATATCCAGACCTTTCGCACCCTCACCAAGTCCATCCTGCCAGGGGCGAGCTT
CACCATCATTGTGCACGCCCTGACGGTGCGGGTGCATGTTGTCGCACTCATATCTAAGATGGACGGCAAA
ACAGGAAACTGGTCGAAGGGGATGGTGAAGTGTGTGCCGCCGGCCGCACAGGCGATGATGCTCTTCCGTG
CTGAGTCGCCTGTCGCCCTCGAACCGGCGACGGAGTGCCGCGCGCTGGGGCGGTTTGTCCTTCAGCAGGA
TGGCGAAACGGTTGCTGGCGGCCTGGTCACACGCGTTGTGGACAAGCCGTG

Protein Sequence : Show Sequence

>gi|146101862|ref|XP_001469224.1| hsp70 subfamily B suppressor 1 [Leishmania infantum JPCM5]
MNRHNKFYAEVAGELEGDDYYGDDDDYNYDEEYEEEGEYDEAAYEATASAAPPEPAHMSESTAQATASAA
PAVRVNPYTTISPQVDDDYELLDMLLPQLHALWKASAPTMLPLSEGEAVTALRASNYDVEPAFLQLKEKR
DEERSKRGGGVLKVTAAAGPANRASTFPAVESPEPGGEEASDNEGNSASPSASSGRTTTTLRGSKGTSQR
RTKQMLEMEPDKEKPDCTFVIAGHVDAGKSTTLGHLLLLLGRVSIQDVERNEKADRTHRKDSFKYAWLLD
QCEEERRRGVTIDSGSFCFETEHRRVHILDAPGHKDFVLSMISSATQADAALLVVTAATSEFETGLHHGT
KSHLLVLKTLGVGSIVVAVNKMDAVAYSQERYDYVVRELQLLLKQTRIPEEAIIGFCPISGMAGVNITQR
GAKETPWYHDLSLIEMIDKCPLESRLLNRPLRLSLQDVQGTTLYAKVESGRLFTGDTVHFVPSEVRVAVK
SIQKPTVAGPVLVAFAGEMVEISTNSSVTGLYPGCVGCEPNLLIHSSTDFEAHIQTFRTLTKSILPGASF
TIIVHALTVRVHVVALISKMDGKTGNWSKGMVKCVPPAAQAMMLFRAESPVALEPATECRALGRFVLQQD
GETVAGGLVTRVVDKP

Molecule Role : Virmugen
Molecule Role Annotation : A Leishmania infantum deletion mutant of HSP70-II gene is attenuated and provides protection against Leishmania infection in the L. major-BALB/c infection model. Also, DeltaHSP70-II is a safe live vaccine as immunodeficient SCID mice, and hamsters, infected with mutant parasites did not develp any sign of pathology (Carrion et al., 2011).
Related Vaccine(s): Leishmania infantum HSP70 II mutant vaccine

5. kmp-11 gene C

Gene Name : kmp-11 gene C
Sequence Strain (Species/Organism) : Leishmania infantum
NCBI Gene ID : 5073121
NCBI Protein GI : CAA64883
Other Database IDs : CDD:281087
GOA:Q25298
InterPro: IPR004132
InterPro: IPR013326
UniProtKB/UniProt: Q25298
Taxonomy ID : 5671
Protein Name : kinetoplastid membrane protein 11
Protein pI : 6.36
Protein Weight : 11620.43
Protein Length : 163
Protein Note : Kinetoplastid membrane protein 11; pfam03037

Protein Sequence : Show Sequence

>CAA64883.1 kinetoplastid membrane protein 11 [Leishmania infantum]
MATTYEEFSAKLDRLDEEFNRKMQEQNAKFFADKPDESTLSPEMKEHYEKFERMIREHTEKFNKKMHEHS
EHFKQKFAELLEQQKAAQYPSK

Molecule Role : Protective antigen
Molecule Role Annotation : (Mortazavidehkordi et al., 2016)

6. LIPO-A

Gene Name : LIPO-A
Sequence Strain (Species/Organism) : Leishmania infantum
VO ID : VO_0011283
NCBI Protein GI : 730579
Other Database IDs : CDD:140267
CDD:240221
Taxonomy ID : 5671
Gene Strand (Orientation) : ?
Protein Name : 60S acidic ribosomal protein P0
Protein pI : 4.83
Protein Weight : 33714.61
Protein Length : 399
Protein Note : 60S acidic ribosomal protein P0. /FTId=PRO_0000154772.

Protein Sequence : Show Sequence

>sp|P39097.1|RLA0_LEIIN RecName: Full=60S acidic ribosomal protein P0
MPSITTAKREYEERLVDCLTKYSCVLFVGMDNVRSQQVHDVGRALRAKAEFMMGKKTLQGKIVEKRAQAK
DASPEAKHFNDQCEEYNLLSGNTGLIFTNNAVQEITSVLDAHRVKRAARVGAISPCDVIVAAGSTGMEPT
QTSFFQALNIATKIAKGMVEIVTEKKVLSVGDKVDNSTATLLQKLNISPFYYQVNVLSVWDRGVLFTRED
LMMTEDMVEKMLMEGLSNVAAMALGAGIPTSSTIGPMLVDAFKNLLAVSVATSYEFEEHNGKELREAAIN
GLLAGSCSAAAEPAAAAPAAPSAAAKEEPEESDEDDFGMGGLF

Molecule Role : Protective antigen
Molecule Role Annotation : Study examined the immunogenic properties of the Leishmania infantum acidic ribosomal protein P0 (LiP0) in the BALB/c mouse model. When mice were immunized with pcDNA3-LiP0, noticeable protection against L. major infection was achieved (Iborra et al., 2003).
Related Vaccine(s): pcDNA3-LiP0

7. P36/LACK

Gene Name : P36/LACK
Sequence Strain (Species/Organism) : Leishmania infantum
VO ID : VO_0011284
NCBI Protein GI : 134085114
Other Database IDs : CDD:238121
CDD:293791
InterPro: IPR001680
InterPro: IPR011046
InterPro: IPR015943
InterPro: IPR017986
InterPro: IPR019775
InterPro: IPR019781
InterPro: IPR019782
InterPro: IPR020472
UniProtKB/UniProt: P62884
Taxonomy ID : 5671
Gene Strand (Orientation) : ?
Protein Name : activated protein kinase c receptor (LACK); p36 LACK protein
Protein pI : 6.77
Protein Weight : 33141.22
Protein Length : 413
Protein Note : guanine nucleotide-binding protein beta subunit-like protein

Protein Sequence : Show Sequence

>CAM69515.1 activated protein kinase c receptor (LACK); p36 LACK protein [Leishmania infantum]
MNYEGHLKGHRGWVTSLACPQQAGSYIKVVSTSRDGTAISWKANPDRHSVDSDYGLPSHRLEGHTGFVSC
VSLAHATDYALTASWDRSIRMWDLRNGQCQRKFLKHTKDVLAVAFSPDDRLIVSAGRDNVIRVWNVAGEC
MHEFLRDGHEDWVSSICFSPSLEHPIVVSGSWDNTIKVWNVNGGKCERTLKGHSNYVSTVTVSPDGSLCA
SGGKDGAALLWDLSTGEQLFKINVESPINQIAFSPNRFWMCVATERSLSVYDLESKAVIAELTPDGAKPS
ECISIAWSADGNTLYSGHKDNLIRVWSISDAE

Molecule Role : Protective antigen
Molecule Role Annotation : BALB/c mice immunized with a DNA vector expressing p36/LACK of Leishmania infantum followed by a booster with VVp36/LACK induced significant protection against Leishmania major infection (Gonzalo et al., 2001).
Related Vaccine(s): VVr expressing L. infantum P36/LACK

8. prohibitin

Gene Name : prohibitin
Sequence Strain (Species/Organism) : Leishmania infantum
NCBI Gene ID : 5068054
NCBI Protein GI : XP_001464650
Other Database IDs : CDD:259799
GOA:A4HX59
InterPro: IPR000163
InterPro: IPR001107
UniProtKB/TrEMBL: A4HX59
Taxonomy ID : 435258
Gene Strand (Orientation) : ?
Protein Name : prohibitin
Protein pI : 8.28
Protein Weight : 28109.152
Protein Length : 328
Protein Note : Prohibitin family; SPFH (stomatin, prohibitin, flotillin, and HflK/C) superfamily; cd03401

Protein Sequence : Show Sequence

>XP_001464650.1 prohibitin [Leishmania infantum JPCM5]
MSKLLQKVAIGAMAAGLSVYSCCFVVYPGEACILYNKISGLKDSVYGEGLQGRIIGLDEVLRFNVRVRPR
TLHTMTGTKDLQMVNVRLRVLFRPMADRLPQIYRTFGLDYDERILPSVSNEILKAVVAEYKAEELIQKRD
AVSARIYQLMQEKVNQFGLIIEDLSLVDIQFGADFMTAVEQKQVAQQEAERYRYVVMENEQKRRAAVVRA
EGEAESARLISEAIQKSGSGLLELRRIEAAVEVANQIVPMQNVTFVPKDANMLMSMSR

Molecule Role : Protective antigen
Molecule Role Annotation : (Dias et al., 2018)

9. SMT

Gene Name : SMT
Sequence Strain (Species/Organism) : Leishmania infantum
VO ID : VO_0011282
NCBI Protein GI : 146104463
Other Database IDs : CDD:332925
CDD:332923
CDD:312111
GOA:A4IDL3
InterPro: IPR013216
InterPro: IPR013705
UniProtKB/TrEMBL: A4IDL3
Taxonomy ID : 435258
Gene Strand (Orientation) : ?
Protein Name : putative sterol 24-c-methyltransferase
Protein pI : 6.62
Protein Weight : 38177.872
Protein Length : 443
Protein Note : 2-polyprenyl-3-methyl-5-hydroxy-6-metoxy-1,4-benzoquinol methylase [Coenzyme transport and metabolism]; cl28104

Protein Sequence : Show Sequence

>XP_001469832.1 putative sterol 24-c-methyltransferase [Leishmania infantum JPCM5]
MSAGGRETAPTNLIRRRNKDETNGDVSAAADRFRDRFEKATLEERKAATTTMVNEYYDLVTDFYEYGWGQ
NFHFAPRYAGETFFESLARHEYFLAARGGFMEGDHIVDVGCGVGGPARNMVRLTRCNVIGVNNNDYQISR
ARRHDALAGMSSKIDYVKTDFCNMSLADNTFDGAYAIEATCHAKDKVKCYSEVFRVIKPGTCFVLYEWCM
TDKYNPNDEYHRTIKHRIELGDGLPEMETCKQVIEYMKQAGFVVEEAIDVISQFESSPIKSIPWYQPLVG
DYSSLQGLRSTPIGRILTNVMCRVLEFVRLAPKGTYKATEILEEAAESLVVGGQLGIFTPSFYIRARKPS
KQA

Molecule Role : Protective antigen
Molecule Role Annotation : Upon challenge with L. infantum, C57BL/6 mice immunized with SMT formulated in MPL-SE adjuvant showed significantly lower parasite burdens in both spleens and livers compared with non-immunized mice or mice injected with adjuvant alone (Goto et al., 2007).
Related Vaccine(s): L. infantum SMT Protein Vaccine

III. Vaccine Related Host Genes

1. 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 infantum HSP70 II mutant vaccine

IV. Vaccine Information

1. A2-CPA-CPB(-CTE)-recombinant L. tarentolae

a. Vaccine Ontology ID:

VO_0004628

b. Type:

Recombinant vector vaccine

c. Status:

Research

d. Host Species for Licensed Use:

Baboon

e. Vector:

(Saljoughian et al., 2013)

f. Preparation

Recombinant L. tarentolae expressing the L. donovani A2 antigen along with cysteine proteinases (CPA and CPB without its unusual C-terminal extension (CPB(-CTE))) as a tri-fusion gene (Saljoughian et al., 2013).

g. Immunization Route

Intramuscular injection (i.m.)

h. Mouse Response

Vaccination Protocol: Group 1 (DNA cSLN/Live) immunized with pcDNA-A2-CPA-CPB-CTE-cSLN (50 µg of pcDNA-A2-CPA-CPB-CTE formulated by cSLN nanoparticles as a chemical delivery as previously described [59] as a prime and with 2×10^7 recombinant L. tarentolae A2-CPA-CPB-CTE as a boost; group 2 (L. tarentolae Live A2-CPA-CPB-CTE/L. tarentolae Live A2-CPA-CPB-CTE) vaccinated with 2×10^7 recombinant L. tarentolae-A2-CPA-CPB-CTE as prime and boost; group 3 (PBS as a control); group 4 [(empty vector pcDNA-cSLN (prime)/Live L. tarentolae wild type (boost) as a control)]; and group 5 (L. tarentolae Live/L. tarentolae Live) vaccinated with 2×10^7 L. tarentolae wild type as prime and boost and used as a control. All groups were immunized via footpad (Saljoughian et al., 2013).
Vaccine Immune Response Type: VO_0003057
Challenge Protocol: Three weeks after the last immunization, all animals were challenged with 10^7 stationary phase L. infantum promastigotes by lateral tail vein (Saljoughian et al., 2013).
Efficacy: Our results showed that immunization with both prime-boost A2-CPA-CPB(-CTE)-recombinant L. tarentolae protects BALB/c mice against L. infantum challenge (Saljoughian et al., 2013).

2. L. infantum H1 protein vaccine

a. Vaccine Ontology ID:

VO_0011350

b. Type:

Subunit vaccine

c. Status:

Research

d. Antigen

L. infantum histone H1

e. Gene Engineering of H1

Type: Recombinant protein preparation
Description: The histone H1 and HASPB1 proteins were purified from endotoxins under pyrogenic free conditions in 1× PBS on a Superose 12 column (Amersham Biosciences) (Moreno et al., 2007).
Detailed Gene Information: Click here.

f. Adjuvant:

VO ID: VO_0001268
Description: Montanide™ ISA 720 (70% formulation, according to manufacturer's instructions, SEPPIC)

g. Immunization Route

Intradermal injection (i.d.)

h. Dog Response

Host Strain: Beagle
Vaccination Protocol: Dogs received three intradermal doses (dorsum; 1 ml/dose) of each vaccine formulation for a period of 3 months. On day 0, dogs from group HASPB1 and group H1 received 100 μg of HASPB1 or histone H1 protein. On days 30 and 60 the dogs received 45 μg of either protein. Dogs in group HASPB1 + H1 received a cocktail of histone H1 and HASPB1 (100 μg each) at day 0, and 45 μg of each protein on days 30 and 60. The adjuvant used for dogs in groups HASPB1, H1 and HASPB1 + H1 was Montanide™ ISA 720 (70% formulation, according to manufacturer's instructions, SEPPIC), given on days 0 and 30. The final immunization on day 60 for groups HASPB1, H1, and HASPB1 + H1 was prepared in the absence of adjuvant to avoid side effects observed following the second dose (Moreno et al., 2007).
Challenge Protocol: Forty-five days following the final immunization, all dogs were infected intravenously with 1 × 10^8 virulent L. infantum promastigotes (Moreno et al., 2007).
Efficacy: Following infection with L. infantum promastigotes, five out of eight beagle dogs immunized with H1 Montanide remained free of clinical signs, compared to two out of eight dogs in the control group. The results demonstrate that H1 antigens with Montanide were able to induce partial protection against canine leishmaniasis, even under extreme experimental challenge conditions (Moreno et al., 2007).

3. L. infantum HASPB1 protein vaccine

a. Vaccine Ontology ID:

VO_0011351

b. Type:

Subunit vaccine

c. Status:

Research

d. Antigen

L. infantum HASPB1

e. Gene Engineering of HASPB1

Type: Recombinant protein preparation
Description: The L. infantum histone H1 was cloned into the pGEX-KG vector (Amersham Biosciences), expressed in Escherichia coli and purified using GST affinity resin (Amersham Biosciences) (Moreno et al., 2007).
Detailed Gene Information: Click here.

f. Adjuvant:

VO ID: VO_0001268
Description: Montanide™ ISA 720 (70% formulation, according to manufacturer's instructions, SEPPIC)

g. Immunization Route

Intradermal injection (i.d.)

h. Dog Response

Host Strain: Beagle
Vaccination Protocol: Dogs received three intradermal doses (dorsum; 1 ml/dose) of each vaccine formulation for a period of 3 months. On day 0, dogs from group HASPB1 and group H1 received 100 μg of HASPB1 or histone H1 protein. On days 30 and 60 the dogs received 45 μg of either protein. Dogs in group HASPB1 + H1 received a cocktail of histone H1 and HASPB1 (100 μg each) at day 0, and 45 μg of each protein on days 30 and 60. The adjuvant used for dogs in groups HASPB1, H1 and HASPB1 + H1 was Montanide™ ISA 720 (70% formulation, according to manufacturer's instructions, SEPPIC), given on days 0 and 30. The final immunization on day 60 for groups HASPB1, H1, and HASPB1 + H1 was prepared in the absence of adjuvant to avoid side effects observed following the second dose (Moreno et al., 2007).
Challenge Protocol: Forty-five days following the final immunization, all dogs were infected intravenously with 1 × 10^8 virulent L. infantum promastigotes (Moreno et al., 2007).
Efficacy: Following infection with L. infantum promastigotes, four out of eight beagle dogs immunized with HASPB1 Montanide remained free of clinical signs, compared to two out of eight dogs in the control group. The results demonstrate that HASPB1 antigens with Montanide were able to induce partial protection against canine leishmaniasis, even under extreme experimental challenge conditions (Moreno et al., 2007).

4. L. infantum SMT Protein Vaccine

a. Vaccine Ontology ID:

VO_0004066

b. Type:

Subunit vaccine

c. Status:

Research

d. Gene Engineering of SMT

Type: Recombinant protein preparation
Description:
Detailed Gene Information: Click here.

e. Adjuvant:

VO ID: VO_0001250
Description: 20 μg of MPL®-SE (GlaxoSmithKline Biologicals, Rixensant, Belgium) (Goto et al., 2007).

f. Immunization Route

subcutaneous injection

g. Mouse Response

Host Strain: C57BL/6
Vaccination Protocol: Mice were immunized with 10 μg of rSMT plus 20 μg of MPL®-SE in a volume of 0.1 ml. Another group of mice was administrated with 10 μg of rSMT alone. Control groups received either saline or MPL®-SE alone. The mice were immunized subcutaneously three times at three weeks intervals in the right hind footpad and at the base of the tail (Goto et al., 2007).
Challenge Protocol: Mice were challenged with L. infantum three weeks after the last immunization. 5 × 10^6 L. infantum promastigotes were suspended in Hank's balanced salt solution and injected i.v. into the tail vein of the mouse (Goto et al., 2007).
Efficacy: Significant reduction of parasites was seen in mice immunized with rSMT plus MPL®-SE compared with those in saline or adjuvant alone groups. The immunized mice showed 43-fold and 55-fold reduction in the number of parasites in spleens, 111-fold and 117-fold reduction in livers compared with saline and adjuvant alone groups, respectively (Goto et al., 2007).

5. Leishmania infantum HSP70 II mutant vaccine

a. Vaccine Ontology ID:

VO_0003006

b. Type:

Live, attenuated vaccine

c. Status:

Research

d. Gene Engineering of HSP70 II

Type: Gene mutation
Description:
Detailed Gene Information: Click here.

e. Preparation

The HSP70-II null mutant (∆hsp70-II::NEO/∆hsp70-II::HYG) is a cloned line that was generated by targeted deletion of both HSP70-II alleles in the L. infantum strain MCAN/ES/96/BCN150 [32]. L. major promastigote (strain MHOM/IL/80/Friedlin; clon V1) were also used in this study. Promastigotes of both species were grown in RPMI 1640 culture medium supplemented with 10% heatinactivated FBS, 100 U/ml penicillin and 100 µg/ml streptomycin (Carrion et al., 2011).

f. Immunization Route

Intraperitoneal injection (i.p.)

g. Mouse Response

Host Strain: BALB/c mouse
Persistence: L. infantum parasites lacking the HSP70-II gene have a virulence greatly reduced (Carrion et al., 2011).
Efficacy: Inoculation of ∆HSP70-II parasites protects BALB/c mice against L. major challenge (Carrion et al., 2011).
Host Gene Response of Ighv1-9
- Gene Response: The IgG2a titers were high for all groups with differing inoculation routes, suggesting that infection with ΔHSP70-II parasites, independent of the inoculation route, leads to a predominant production of anti-Leishmania antibodies of the IgG2a isotope. Antibody titers were determined by ELISA before and 4 weeks after inoculation and showed an increase between the two samples. IgG2a titers were significantly higher than IgG1 titers (Carrion et al., 2011).
- Detailed Gene Information: Click here.

6. pcDNA3-LiP0

a. Product Name:

DNA Vaccine encoding LIPO-A Protein of L. infantum

b. Vaccine Ontology ID:

VO_0004197

c. Type:

DNA vaccine

d. Status:

Research

e. Antigen

LiP0

f. Gene Engineering of LIPO-A

Type: DNA vaccine construction
Description:
Detailed Gene Information: Click here.

g. Vector:

Eukaryotic expression plasmid pcDNA3 (Invitrogen, San Diego, Calif.) (Iborra et al., 2003)

h. Immunization Route

Intramuscular injection (i.m.)

i. Mouse Response

Host Strain: BALB/c
Vaccination Protocol: In DNA immunization experiments, mice were inoculated twice intramuscularly (i.m.) in both quadriceps with 100 μg of DNA (50 μg per leg) of either pcDNA3-LiP0 or pcDNA3 (controls) in a total volume of 100 μl of PBS. When “prime-boost” immunization was carried out, two inoculations of DNA and two inoculations of recombinant protein were administered. In all groups, the mice were inoculated at 2-week intervals (Iborra et al., 2003).
Challenge Protocol: Two weeks after the final inoculation, immunized mice were challenged with 5 × 10^4 stationary-phase promastigotes of L. major that were suspended in 50 μl of PBS and injected into the left hind footpad (Iborra et al., 2003).
Efficacy: Three weeks after challenge, the parasite burden was found to be significantly lower in mice vaccinated with pcDNA3-LiP0 than in controls. Mice vaccinated with LiP0-DNA had a 99.1% reduction in the parasite burden 3 weeks after infection compared with mice vaccinated with control DNA (Iborra et al., 2003).

7. VVr expressing L. infantum P36/LACK

a. Vaccine Ontology ID:

VO_0004198

b. Type:

Recombinant vector vaccine

c. Status:

Research

d. Antigen

L. infantum p36/LACK protein

e. Gene Engineering of P36/LACK

Type: Recombinant vector construction
Description: The gene encoding L. infantum p36/LACK protein was expressed by recombinant vaccinia virus, and co-expressed murine IL-12 (Gonzalo et al., 2001).
Detailed Gene Information: Click here.

f. Adjuvant:

VO ID: VO_0001147

g. Vector:

Recombinant vaccinia virus (VVr) derived from the wild-type Western Reserve strain (WR) (Gonzalo et al., 2001).

h. Immunization Route

Intraperitoneal injection (i.p.)

i. Mouse Response

Host Strain: BALB/c
Vaccination Protocol: Mice were primed with VVr (5 × 10^7 PFU/mouse) by the intraperitoneal (i.p.) route. Two weeks later (14 days p.i.), animals were boosted with VVr or recombinant p36 antigen (Gonzalo et al., 2001).
Challenge Protocol: 35 days p.i., mice were challenged in the right hind foot with 10^5 of L. major stationary-phase promastigote culture (Gonzalo et al., 2001).
Efficacy: BALB/c mice immunized with a DNA vector expressing p36/LACK of Leishmania infantum followed by a booster with VVp36/LACK induced significant protection against Leishmania major infection (Gonzalo et al., 2001).

V. References

1. Carrion et al., 2011: Carrion J, Folgueira C, Soto M, Fresno M, Requena JM. Leishmania infantum HSP70-II null mutant as candidate vaccine against leishmaniasis: a preliminary evaluation. Parasites & vectors. 2011; 4(1); 150. [PubMed: 21794145].

2. Dias et al., 2018: Dias DS, Ribeiro PAF, Martins VT, Lage DP, Ramos FF, Dias ALT, Rodrigues MR, Portela �SB, Costa LE, Caligiorne RB, Steiner BT, Ch�vez-Fumagalli MA, Salles BCS, Santos TTO, Silveira JAG, Magalh�es-Soares DF, Roatt BM, Machado-de-�vila RA, Duarte MC, Menezes-Souza D, Silva ES, Galdino AS, Coelho EAF. Recombinant prohibitin protein of Leishmania infantum acts as a vaccine candidate and diagnostic marker against visceral leishmaniasis. Cellular immunology. 2018; 323; 59-69. [PubMed: 29128045].

3. Gonzalo et al., 2001: Gonzalo RM, Rodríguez JR, Rodríguez D, González-Aseguinolaza G, Larraga V, Esteban M. Protective immune response against cutaneous leishmaniasis by prime/booster immunization regimens with vaccinia virus recombinants expressing Leishmania infantum p36/LACK and IL-12 in combination with purified p36. Microbes and infection / Institut Pasteur. 2001; 3(9); 701-711. [PubMed: 11489418].

4. Goto et al., 2007: Goto Y, Bogatzki LY, Bertholet S, Coler RN, Reed SG. Protective immunization against visceral leishmaniasis using Leishmania sterol 24-c-methyltransferase formulated in adjuvant. Vaccine. 2007; 25(42); 7450-7458. [PubMed: 17804125].

5. Iborra et al., 2003: Iborra S, Soto M, Carrión J, Nieto A, Fernández E, Alonso C, Requena JM. The Leishmania infantum acidic ribosomal protein P0 administered as a DNA vaccine confers protective immunity to Leishmania major infection in BALB/c mice. Infection and immunity. 2003; 71(11); 6562-6572. [PubMed: 14573678].

6. Moreno et al., 2007: Moreno J, Nieto J, Masina S, Cañavate C, Cruz I, Chicharro C, Carrillo E, Napp S, Reymond C, Kaye PM, Smith DF, Fasel N, Alvar J. Immunization with H1, HASPB1 and MML Leishmania proteins in a vaccine trial against experimental canine leishmaniasis. Vaccine. 2007; 25(29); 5290-5300. [PubMed: 17576026].

7. Mortazavidehkordi et al., 2016: Mortazavidehkordi N, Farjadfar A, Khanahmad H, Ghayour Najafabadi Z, Hashemi N, Fallah A, Najafi A, Kia V, Hejazi SH. Evaluation of a novel lentiviral vaccine expressing KMP11-HASPB fusion protein against Leishmania infantum in BALB/c mice. Parasite immunology. 2016; 38(11); 670-677. [PubMed: 27540714].

8. Saljoughian et al., 2013: Saljoughian N, Taheri T, Zahedifard F, Taslimi Y, Doustdari F, Bolhassani A, Doroud D, Azizi H, Heidari K, Vasei M, Namvar Asl N, Papadopoulou B, Rafati S. Development of novel prime-boost strategies based on a tri-gene fusion recombinant L. tarentolae vaccine against experimental murine visceral leishmaniasis. PLoS neglected tropical diseases. 2013; 7(4); e2174. [PubMed: 23638195].

9. Wiki: Leishmania infantum: Leishmania infantum [http://en.wikipedia.org/wiki/Leishmania_infantum]