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Leishmania infantum

Table of Contents
  1. General Information
    1. NCBI Taxonomy ID
    2. Disease
    3. Introduction
    4. Microbial Pathogenesis
    5. Host Ranges and Animal Models
    6. Host Protective Immunity
  2. Vaccine Related Pathogen Genes
    1. H1 (Protective antigen)
    2. HASPB1 (Protective antigen)
    3. LIPO-A (Protective antigen)
    4. P36/LACK (Protective antigen)
    5. SMT (Protective antigen)
    6. HSP70 II (Virmugen)
  3. Vaccine Related Host Genes
    1. Ighv1-9
  4. Vaccine Information
    1. A2-CPA-CPB(-CTE)-recombinant L. tarentolae
    2. L. infantum H1 protein vaccine
    3. L. infantum HASPB1 protein vaccine
    4. L. infantum SMT Protein Vaccine
    5. Leishmania infantum HSP70 II mutant vaccine
    6. pcDNA3-LiP0
    7. VVr expressing L. infantum P36/LACK
  5. 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).
1. H1
  • Gene Name : H1
  • Sequence Strain (Species/Organism) : Leishmania infantum
  • VO ID : VO_0011285
  • NCBI Nucleotide GI : 78146499
  • NCBI Protein GI : 78146500
  • Protein Accession : ABB22792.1
  • Taxonomy ID : 5671
  • Gene Strand (Orientation) : ?
  • Protein Name : histone H1
  • Protein Length : 107
  • 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
    >gi|78146500|gb|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. HASPB1
  • Gene Name : HASPB1
  • Sequence Strain (Species/Organism) : Leishmania infantum
  • VO ID : VO_0011286
  • NCBI Nucleotide GI : 3724133
  • NCBI Protein GI : 3724134
  • Protein Accession : CAA09789.1
  • Other Database IDs : CDD:171655
    CDD:162113
    InterPro: IPR008165
    UniProtKB/TrEMBL: O77301
  • Taxonomy ID : 5661
  • Gene Strand (Orientation) : ?
  • Protein Name : HASPB1 protein
  • Protein Length : 401
  • Protein Note : transcription termination factor Rho; Provisional; PRK12678
  • 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
    >gi|3724134|emb|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
3. 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
4. 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:88595
  • Taxonomy ID : 5671
  • Gene Strand (Orientation) : ?
  • Protein Name : 60S acidic ribosomal protein P0
  • Protein Length : 323
  • Protein Note : 60S acidic ribosomal protein P0. /FTId=PRO_0000154772.
  • Protein Sequence : Show Sequence
    >gi|730579|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
5. P36/LACK
  • Gene Name : P36/LACK
  • Sequence Strain (Species/Organism) : Leishmania infantum
  • VO ID : VO_0011284
  • NCBI Protein GI : 134085114
  • Other Database IDs : CDD:29257
    GOA:A4I408
    InterPro: IPR001680
    InterPro: IPR011046
    UniProtKB/TrEMBL: A4I408
  • Taxonomy ID : 5671
  • Gene Strand (Orientation) : ?
  • Protein Name : activated protein kinase c receptor (LACK); p36 LACK protein
  • Protein Length : 312
  • Protein Note : guanine nucleotide-binding protein beta subunit-like protein
  • Protein Sequence : Show Sequence
    >gi|134085114|emb|CAM69515.1| activated protein kinase c receptor (LACK); p36 LACK protein; guanine nucleotide-binding protein beta subunit-like 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
6. SMT
  • Gene Name : SMT
  • Sequence Strain (Species/Organism) : Leishmania infantum
  • VO ID : VO_0011282
  • NCBI Protein GI : 146104463
  • Other Database IDs : CDD:32411
    CDD:100107
    CDD:149521
  • Taxonomy ID : 435258
  • Gene Strand (Orientation) : ?
  • Protein Name : sterol 24-c-methyltransferase
  • Protein Length : 353
  • Protein Note : Cyclopropane fatty acid synthase and related methyltransferases [Cell envelope biogenesis, outer membrane]; COG2230
  • Protein Sequence : Show Sequence
    >gi|146104463|ref|XP_001469832.1| sterol 24-c-methyltransferase [Leishmania infantum]
    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
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 2×107 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 2×107 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 2×107 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 107 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: Montanide ISA 720
  • 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 × 108 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: Montanide ISA 720
  • 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 × 108 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: MPL vaccine adjuvant
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 × 106 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 × 104 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: IL-12 vacince adjuvant
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 × 107 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 105 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. 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].
3. 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].
4. 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].
5. 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].
6. 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].
7. Wiki: Leishmania infantum: Leishmania infantum [http://en.wikipedia.org/wiki/Leishmania_infantum]