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Leishmania major

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. Cpa (Protective antigen)
    2. Cpb (Protective antigen)
    3. Gp63 (Protective antigen)
    4. H2B (Protective antigen)
    5. KMP-11 (Protective antigen)
    6. LACK (Protective antigen)
    7. LmSTI1 (Protective antigen)
    8. PSA-2 (Protective antigen)
    9. SP (Protective antigen)
    10. SW3.1 (Protective antigen)
    11. TSA (Protective antigen)
  3. Vaccine Information
    1. L. major DNA Vaccine encoding Gp63
    2. L. major DNA Vaccine encoding LACKp24, TSA, LmSTI1 and CPa
    3. L. major DNA Vaccine encoding SP
    4. L. major DNA vaccine pcLACK + IL-22
    5. L. major H1 Protein Vaccine
    6. L. major H2B Protein Vaccine
    7. L. major PSA-2 Protein Vaccine
    8. L. T -PpSP15
    9. Leishmania major DNA vaccine KMP-11
    10. SL3261-L. major
  4. References
I. General Information
1. NCBI Taxonomy ID:
5664
2. Disease:
Cutaneous leishmaniasis
3. Introduction
Leishmania parasites belonging to the order Kinetoplastida are the causative agents of a large spectrum of diseases, leishmaniasis, varying from localized cutaneous to visceral leishmaniasis, the later being often fatal if not treated. Leishmaniasis with a total number of 12 million cases, and 350 million at risk is a major health problem in several tropical and subtropical areas, and its control relies still most frequently on pentavalent antimony-containing drug chemotherapy. The effectiveness of these compounds however is eroded by the emergences of parasite resistance to the drug. Therefore, other strategies, such as vaccination, need to be developed for a better control of leishmaniasis. Mouse models of cutaneous leishmaniasis have been extensively used to explore the requirements for effective vaccination, namely vaccination which prevent at least the disease stage to be reached (Rafati et al., 2002).
4. Microbial Pathogenesis
The establishment of the primary leishmania infection and development of clinical disease depend on parasite, host, and sandfly factors; dose or route of inoculation; and the maintenance of macrophages in an inert, deactivated state. Pathogenesis follows a complex set of interactions between many factors triggered by the host's innate and acquired immune responses (eg, macrophages, neutrophils, natural killer cells, dendritic cells). These inflammatory responses mediate disease expression and may result in either symptomless or subclinical infection, self-healing LCL, or chronic leishmaniasis (eg, DCL, mucosal leishmaniasis, leishmaniasis recidivans). Clinical cure ensues when macrophages become activated to a leishmanicidal state.
When biting their hosts, infected sandflies regurgitate leishmania promastigotes into the skin, which invade or are phagocytosed by local or recruited host cells, mainly macrophages. Within the phagolysosomes of resident macrophages, promastigotes become amastigotes. Amastigotes replicate and may then infect additional macrophages, either locally or in distant tissues after dissemination. When blood-feeding on an infected host, naive sandflies become infected with amastigotes, which transform back into promastigotes in the sandfly's gut (depending on Leishmania spp, different regions of the gut will be parasitised. The parasites then migrate to the sandfly's proboscis, thus completing the leishmania life cycle (Reithinger et al., 2007).
5. Host Ranges and Animal Models
Leishmania major is vectored by the sandfly and can infect humans and other mammals. Natural leishmania infections are found in a range of non-human mammal hosts (mainly marsupials, rodents, edentates, and carnivores) (Reithinger et al., 2007).
6. Host Protective Immunity
The immune response to Leishmania infection is cell-mediated, and the clinical outcome is dependent on host-mediated T helper (Th)1 or Th2 responses. A Th1 response mediated by interferon (IFN)-γ, tumour necrosis factor and interleukin (IL)-12 is associated with disease resolution and resistance, and a Th2 IL-4-producing response confers disease susceptibility and progression (Ameen, 2010).
1. Cpa
  • Gene Name : Cpa
  • Sequence Strain (Species/Organism) : Leishmania major
  • VO ID : VO_0011275
  • NCBI Nucleotide GI : 71084305
  • NCBI Protein GI : 71084306
  • Protein Accession : AAZ23598.1
  • Other Database IDs : CDD:157580
    CDD:30292
  • Taxonomy ID : 5664
  • Gene Strand (Orientation) : ?
  • Protein Name : cysteine protease
  • Protein Length : 327
  • Protein Note : Cathepsin propeptide inhibitor domain (I29); cl07031
  • DNA Sequence : Show Sequence
    >gi|71084305|gb|DQ071680.1| Leishmania major cysteine protease (Cpa) gene, partial cds
    AAAACACCTCTCGGTGTCGACAACTTCATTGCCTCAGCACATTACGGACGCTTTAAGGAGCGCCACGGCA
    AGTCCTTCGGCGAGGACGCCGATGAGGGTCACCGCTTCAATGCCTTCAAGCAGAACATGCAGACCGCCTA
    CTTCCTCAACACGCACAACCCGCACGCGCACTACGACGTGTCCGGCAAGTTTGCAGACCTCACCCCCCAG
    GAGTTCGCCAAGCTGTACCTGAACCCCGACTACTACGCGCGCCGCGGTAAGGATTACAAGGAGCACGTGC
    ACGTCGACGACAGCGTCCTCAGTGGTGCGATGTCGGTGGACTGGCGTGAGAAGGTTGCCGTGACGCCGGT
    GAAGAACCAGGGAATGTGCGGCTCGTGCTGGGCTTTCTCCGCCATTGGCAACATTGAAAGTCAGTGGGCT
    TTGAAAAACCACTCGCTGGTTTCGCTGTCGGAGCAGATGCTCGTGTCATGCGACGACATCGATGATGGGT
    GCAACGGTGGGCTGATGGACCAGGCGATGGAATGGATCATCCAACATCACAACGGCACTGTGCCCACGGA
    GGAAAGCTACCCCTACGCCTCTGCCGGCGGCACGAGCCCGCCGTGCCATGACAAAGGCGAGTTTGGCGCC
    AGAATCAGTGGTTACATGTCCCTGCCGCATGACGAGAAGGCGATCGCGGCTTATGTGGAGAAGAAAGGCC
    CCGTCGCTGTCGCCGTCGACGCGACAACCTGGCAGCTGTACTTTGGCGGTGTGGTCACGCTCTGCTTCGG
    GTGGTCGCTCAACCACGGTGTGCTCGTTGTCGGCTTCAACAAAAGAGCGAAACCGCCGTACTGGATCGTG
    AAGAACTCGTGGGGCACCTCGTGGGGTGAGAAGGGGTACATCCGCCTTGCCATGGGCAGCAACCAGTGCT
    TGCTGAAGAATTACCCTGTGACGGCCACGGTTGACGACTCAAACACCTCTCCCGTGCCGACGACACCGGC
    CTAG
  • Protein Sequence : Show Sequence
    >gi|71084306|gb|AAZ23598.1| cysteine protease [Leishmania major]
    KTPLGVDNFIASAHYGRFKERHGKSFGEDADEGHRFNAFKQNMQTAYFLNTHNPHAHYDVSGKFADLTPQ
    EFAKLYLNPDYYARRGKDYKEHVHVDDSVLSGAMSVDWREKVAVTPVKNQGMCGSCWAFSAIGNIESQWA
    LKNHSLVSLSEQMLVSCDDIDDGCNGGLMDQAMEWIIQHHNGTVPTEESYPYASAGGTSPPCHDKGEFGA
    RISGYMSLPHDEKAIAAYVEKKGPVAVAVDATTWQLYFGGVVTLCFGWSLNHGVLVVGFNKRAKPPYWIV
    KNSWGTSWGEKGYIRLAMGSNQCLLKNYPVTATVDDSNTSPVPTTPA
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Researchers evaluated the potency of different DNA vaccine candidates in BALB/c mice using high dose footpad parasite challenge with L. major. Mice inoculated pCMV3ISS-CPa developed significantly smaller lesions in their footpads after challenge with the parasite. The vaccine was able to induce a partially protective effect (Ahmed et al., 2009).
  • Related Vaccine(s): L. major DNA Vaccine encoding LACKp24, TSA, LmSTI1 and CPa
2. Cpb
  • Gene Name : Cpb
  • Sequence Strain (Species/Organism) : Leishmania major
  • VO ID : VO_0011281
  • NCBI Protein GI : 54287314
  • Other Database IDs : CDD:30292
    GOA:Q5ZQK2
    HSSP: P07711
    InterPro: IPR000169
    InterPro: IPR000668
    InterPro: IPR013128
    UniProtKB/TrEMBL: Q5ZQK2
  • Taxonomy ID : 5664
  • Gene Strand (Orientation) : ?
  • Protein Name : cysteine proteinase b
  • Protein Length : 174
  • Protein Note : Peptidase C1A subfamily (MEROPS database nomenclature); composed of cysteine peptidases (CPs) similar to papain, including the mammalian CPs (cathepsins B, C, F, H, L, K, O, S, V, X and W). Papain is an endopeptidase with specific substrate preferences...; cd02248
  • Protein Sequence : Show Sequence
    >gi|54287314|emb|CAD54749.1| cysteine proteinase b [Leishmania major]
    NQGACGSCWAFSAVGNIESQWAVAGHKLVRLSEQQLVSCDHVDNGCGGGLMLQAFEWVLRNMNGTVFTEK
    SYPYVSGNGDVPECSNSSELAPGARIDGYVSMESSERVMAAWLAKNGPISIAVDASSFMSYHSGVLTSCI
    GEQLNHGVLLVGYNMTGEVPYWVIKNSWGEDWGE
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Together with poloxamer 407 as adjuvant the recombinant type I (rCPB) cysteine proteinase of Leishmania major was screened as a potential vaccines against L. major in a mouse model. Using the footpad thickness increase to monitor the clinical outcome/cutaneous lesion at site of L. major delivery, it was possible to document that rCPB allowed BALB/c mice to mount a partial protective response (Rafati et al., 2002).
3. Gp63
  • Gene Name : Gp63
  • Sequence Strain (Species/Organism) : Leishmania major
  • VO ID : VO_0011278
  • NCBI Protein GI : 259011719
  • 3D structure: PDB ID : 1LML
  • Other Database IDs : CDD:141732
  • Taxonomy ID : 5664
  • Gene Strand (Orientation) : ?
  • Protein Name : GP63
  • Protein Length : 602
  • Protein Note : Leishmanolysin; cl03222
  • Protein Sequence : Show Sequence
    >gi|259011719|gb|ACL01096.2| GP63 [Leishmania major]
    MSVDSSSTHRRRCVAARLVRLAAAGAAVTVAVGTAAAWAHAGALQHRCVHDAMQARVRQSVADHHKAPGA
    VSAVGLPYVTLDAAHTAAAADPRPGSARSVVRDVNWGALRIAVSTEDLTDPAYHCARVGQHVKDHAGAIA
    ICTAEDILTNEKRDILVKHLIPQAVQLHTERLKVQQVQGKWKVTDMVGDICGDFKVPQAHITEGFSNTDF
    VMYVASVPSEEGVLAWATTCQTFSDGHPAVGVINIPAANIASRYDQLVTRVVTHEMAHALGFSGPFFEDA
    RIVASVPNVRGKNFDVPVINSSTAVAKAREQYGCDTLEYLEVEDQGGAGSAGSHIKMRNAQDELMAPAAA
    AGYYTALTMAIFQDLGFYQADFSKAEVMPWGQNAGCAFLTNKCMEQSVTQWPAMFCNESEDAIRCPTSRL
    SLGACGVTRHPGLPPYWQYFTDPSLAGVSAFMDYCPVVVPYSDGSCTQRASEAHASLLPFNVFSDAARCI
    DGAFRPKATDGIVKSYAGLCANVQCDTATRTYSVQVHGSNDYTNCTPGLRVELSTVSNAFEGGGYITCPP
    YVEVCQGNVQAAKDGGNTAAGRRGPRAAATALLVAALLAVAL
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Cell-mediated immunity to Leishmania major (L. major) was induced by injecting BALB/c mice intradermally with plasmid DNA expressing the conserved L. major cell surface glycoprotein gp63 (gp63-pcDNA-3). Challenge studies revealed that gp63-pcDNA-3 vaccination protected 30% of susceptible mice (21 of 70) from Leishmania infection (Walker et al., 1998).
  • Related Vaccine(s): L. major DNA Vaccine encoding Gp63
4. H2B
  • Gene Name : H2B
  • Sequence Strain (Species/Organism) : Leishmania major
  • VO ID : VO_0011277
  • NCBI Protein GI : 13384083
  • Other Database IDs : CDD:173994
  • Taxonomy ID : 5664
  • Gene Strand (Orientation) : ?
  • Protein Name : histone H2B
  • Protein Length : 111
  • Protein Note : Histone 2A; H2A is a subunit of the nucleosome. The nucleosome is an octamer containing two H2A, H2B, H3, and H4 subunits. The H2A subunit performs essential roles in maintaining structural integrity of the nucleosome, chromatin condensation, and...; cl00074
  • Protein Sequence : Show Sequence
    >gi|13384083|gb|AAK21263.1|AF336276_1 histone H2B [Leishmania major]
    MASSRSASRKASNPHKSHRKPKRSWNVYVGRSLKAINAQMSMSHRTMKIVNSYVNDVMERICTEAASIVR
    ANKKRTLGAREVQTAVRIVLPAELAKHAMAEGTKAVSSASA
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Researchers tested the ability of the entire H2B protein of L. major, its divergent or conserved regions to provide protection against virulent L. major challenge. The divergent amino-terminal region of H2B is able to confer potent protection against a virulent challenge in BALB/c mice (Chenik et al., 2006).
  • Related Vaccine(s): L. major H2B Protein Vaccine
5. KMP-11
  • Gene Name : KMP-11
  • Sequence Strain (Species/Organism) : Leishmania donovani
  • NCBI Protein GI : 34922492
  • Other Database IDs : CDD:111880
  • Taxonomy ID : 5661
  • Gene Strand (Orientation) : ?
  • Protein Name : Kinetoplastid membrane protein 11
  • Protein Length : 92
  • Protein Note : Lipophosphoglycan-associated protein; LPGAP
  • Protein Sequence : Show Sequence
    >gi|34922492|sp|Q36736.1|KM11_LEIDO RecName: Full=Kinetoplastid membrane protein 11; Short=KMP-11; AltName: Full=Lipophosphoglycan-associated protein; Short=LPGAP
    MATTYEEFSAKLDRLDQEFNRKMQEQNAKFFADKPDESTLSPEMREHYEKFERMIKEHTEKFNKKMHEHS
    EHFKQKFAELLEQQKAAQYPSK
  • Molecule Role : Protective antigen
  • Related Vaccine(s): Leishmania major DNA vaccine KMP-11 , SL3261-L. major
6. LACK
  • Gene Name : LACK
  • Sequence Strain (Species/Organism) : Leishmania major
  • VO ID : VO_0011260
  • NCBI Nucleotide GI : 1276476
  • NCBI Protein GI : 1276477
  • Protein Accession : AAA97577.1
  • Other Database IDs : CDD:29257
  • Taxonomy ID : 5664
  • Gene Strand (Orientation) : ?
  • Protein Name : LACK
  • Protein Length : 312
  • Protein Note : WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues...; cd00200
  • DNA Sequence : Show Sequence
    >gi|1276476|gb|U27568.1|LMU27568 Leishmania major activated protein kinase C receptor homolog LACK mRNA, complete cds
    AACTAACGCTATATAAGTATCAGTTTCTGTACTTTATTGATAAGTTTCTTCTCACTCCACTTCGTTTCAC
    CATGAACTACGAGGGTCACCTGAAGGGTCACCGAGGATGGGTCACCTCCCTGGCCTGCCCGCAGCAGGCG
    GGGTCGTACATCAAGGTGGTGTCGACGTCGCGCGATGGTACGGTCATCTCGTGGAAGGCCAACCCCGACC
    GCCACAGCGTGGACAGCGACTACGGTCTGCCGAACCACCGCCTCGAGGGCCACACCGGCTTCGTGTCGTG
    CGTGTCGCTGGCCCACGCCACCGACTACGCGCTGACCGCGTCCTGGGACCGCTCCATCCGCATGTGGGAC
    CTGCGCAATGGCCAGTGCCAGCGCAAGTTCCTGAAGCACACCAAGGACGTGCTCGCCGTCGCCTTCTCGC
    CGGACGACCGCCTGATCGTGTCCGCGGGCCGCGACAACGTGATCCGCGTGTGGAACGTGGCGGGTGAGTG
    CATGCACGAGTTCCTGCGCGACGGCCACGAGGACTGGGTGAGCAGCATCTGCTTCTCGCCGTCGCTGGAG
    CACCCGATCGTGGTGTCCGGCAGCTGGGACAACACCATCAAAGTATGGAACGTGAACGGGGGCAAGTGTG
    AGCGCACGCTCAAGGGCCACAGCAACTACGTGTCCACGGTGACGGTGTCGCCAGACGGGTCTCTGTGCGC
    ATCTGGCGGCAAGGACGGCGCGGCGCTGTTGTGGGACCTGAGCACCGGTGAGCAGCTGTTCAAGATCAAC
    GTGGAGTCGCCCATCAACCAGATCGGCTTCTCGCCCAACCGCTTCTGGATGTGCGTCGCGACGGAGAGGT
    CTCTGTCCGTGTACGACCTGGAGAGCAAGGCCGTGATTGCGGAGCTGACGCCGGACGGCGCGAAGCCGTC
    GGAGTGCATCTCCATTGCCTGGTCCGCCGACGGCAACACTCTGTACTCCGGCCACAAGGACAACCTGATC
    CGCGTGTGGTCCATCTCCGACGCCGAGTAATGGCCGCGCGCTGCTCGTGCCGGACGGCGTGGTAGGCGAG
    GGAGAACGAGCGAGAAGTGA
  • Protein Sequence : Show Sequence
    >gi|1276477|gb|AAA97577.1| LACK [Leishmania major]
    MNYEGHLKGHRGWVTSLACPQQAGSYIKVVSTSRDGTVISWKANPDRHSVDSDYGLPNHRLEGHTGFVSC
    VSLAHATDYALTASWDRSIRMWDLRNGQCQRKFLKHTKDVLAVAFSPDDRLIVSAGRDNVIRVWNVAGEC
    MHEFLRDGHEDWVSSICFSPSLEHPIVVSGSWDNTIKVWNVNGGKCERTLKGHSNYVSTVTVSPDGSLCA
    SGGKDGAALLWDLSTGEQLFKINVESPINQIGFSPNRFWMCVATERSLSVYDLESKAVIAELTPDGAKPS
    ECISIAWSADGNTLYSGHKDNLIRVWSISDAE
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Researchers evaluated the potency of different DNA vaccine candidates in BALB/c mice using high dose footpad parasite challenge. A truncated portion of the LACK antigen (LACKp24) was able to induce the highest protective effect compared to other constructs. The DNA vaccine encoding LACK was able to induce partial protection in mice (Ahmed et al., 2009).
  • Related Vaccine(s): L. major DNA Vaccine encoding LACKp24, TSA, LmSTI1 and CPa , L. major DNA vaccine pcLACK + IL-22
7. LmSTI1
  • Gene Name : LmSTI1
  • Sequence Strain (Species/Organism) : Leishmania major
  • VO ID : VO_0011274
  • NCBI Nucleotide GI : 1698879
  • NCBI Protein GI : 1698880
  • Protein Accession : AAB37318.1
  • Other Database IDs : CDD:29151
    CDD:128966
  • Taxonomy ID : 5664
  • Gene Strand (Orientation) : ?
  • Protein Name : protein antigen LmSTI1
  • Protein Length : 545
  • Protein Note : Tetratricopeptide repeat domain; typically contains 34 amino acids [WLF]-X(2)-[LIM]-[GAS]-X(2)-[YLF]-X(8)-[ASE]-X(3)-[FYL]- X(2)-[ASL]-X(4)-[PKE] is the consensus sequence; found in a variety of organisms including bacteria, cyanobacteria, yeast, fungi...; cd00189
  • DNA Sequence : Show Sequence
    >gi|1698879|gb|U73845.1|LMU73845 Leishmania major protein antigen LmSTI1 mRNA, partial cds
    TGGACGCAACTGAGCTGAAGAACAAGGGGAACGAAGAGTTCTCCGCCGGCCGCTATGTGGAGGCGGTGAA
    CTACTTCTCAAAGGCGATCCAGTTGGATGAGCAGAACAGTGTCCTCTACAGCAACCGCTCCGCCTGTTTT
    GCAGCCATGCAGAAATACAAGGACGCGCTGGACGACGCCGACAAGTGCATCTCGATCAAGCCGAATTGGG
    CCAAGGGCTACGTGCGCCGAGGAGCAGCTCTCCATGGCATGCGCCGCTACGACGATGCCATTGCCGCGTA
    TGAAAAGGGGCTCAAGGTGGACCCTTCCAACAGCGGCTGCGCGCAGGGCGTGAAGGACGTGCAGGTAGCC
    AAGGCCCGCGAAGCACGTGACCCCATCGCTCGCGTCTTCACCCCGGAGGCGTTCCGCAAGATCCAAGAGA
    ATCCCAAGCTGTCTCTACTTATGCTGCAGCCGGACTACGTGAAGATGGTAGACACCGTCATCCGCGACCC
    TTCGCAGGGCCGGCTGTACATGGAAGACCAGCGCTTTGCCCTGACGCTCATGTACCTGAGCGGAATGAAG
    ATTCCCAACGATGGTGATGGCGAGGAGGAGGAACGTCCGTCTGCGAAGGCGGCAGAGACAGCGAAGCCAA
    AAGAGGAGAAGCCTCTCACCGACAACGAGAAGGAGGCCCTGGCGCTCAAGGAGGAGGGCAACAAGCTGTA
    CCTCTCGAAGAAGTTTGAGGAGGCGCTGACCAAGTACCAAGAGGCGCAGGTGAAAGACCCCAACAACACT
    TTATACATTCTGAACGTGTCGGCCGTGTACTTCGAGCAGGGTGACTACGACAAGTGCATCGCCGAGTGCG
    AGCACGGTATCGAGCACGGTCGCGAGAACCACTGCGACTACACAATCATTGCGAAGCTCATGACCCGGAA
    CGCCTTGTGCCTCCAGAGGCAGAGGAAGTACGAGGCTGCTATCGACCTTTACAAGCGCGCCCTTGTCGAG
    TGGCGTAACCCTGACACCCTCAAGAAGCTGACGGAGTGCGAGAAGGAGCACCAAAAGGCGGTGGAGGAAG
    CCTACATCGATCCTGAGATCGCGAAGCAGAAGAAAGACGAAGGTAACCAGTACTTCAAGGAGGATAAGTT
    CCCCGAGGCCGTGGCAGCGTACACGGAGGCCATCAAGCGCAACCCTGCCGAGCACACCTCCTACAGCAAT
    CGCGCGGCCGCGTACATCAAGCTTGGAGCCTTCAACGACGCCCTCAAGGACGCGGAGAAGTGCATTGAGC
    TGAAGCCCGACTTTGTTAAGGGCTACGCGCGCAAGGGTCATGCTTACTTTTGGACCAAGCAGTACAACCG
    CGCGCTGCAGGCGTACGATGAGGGCCTCAAGGTGGACCCGAGCAATGCGGACTGCAAGGATGGGCGGTAT
    CGCACAATCATGAAGATTCAGGAGATGGCATCTGGCCAATCCGCGGATGGCGACGAGGCGGCGCGCCGGG
    CCATGGACGATCCTGAAATCGCGGCAATCATGCAAGATAGCTACATGCAACTAGTGTTGAAGGAGATGCA
    GAACGATCCCACGCGCATTCAGGAGTACATGAAGGACTCCGGGATCTCATCGAAGATCAACAAGCTGATT
    TCAGCTGGCATCATTCGTTTTGGTCAGTAGACTTCTACGCTGCCTCATCTTTTCCGTGTCTTTGCGTCGG
    CGGGTATCGTAAAGCACAATAAAGCAGCGATTCACATGCACGAGTAAAGTGCTGCGCCTCTCAAACACGA
    CGTCGAGGCTGTGGTGCAGATGCGCGTCCTGCATGAAGGTAGTGAAGAGGAAAGTAAGGGATGTTGTTTG
    TGGGCCTTCGTGGCTGCGCACACACCTCTTATCTCCTTCGCTTGGTACCTTCTCCCTTTTTCGTCTTCAC
    CCCCCTTTCTCTTCTCACGCTCTCCCTGGCGCGGTGGTGCAACGATTTCGTTTTATTTACGTCTGTGTAG
    CTCCTCTATTCAACGGTGCGATGACGCTAACGAAGCTGGCCTGTATTCGGCTAAGGCGAAGGCAAAAGAC
    TAGGAGGGGGGGGGGAAGGAGACGGCGTGACCATCACTGCGAAGAAACAAGCCGAAGAAAAGGCCCCGAA
    CGCCTGCATTTCCGCGCGCCCTCGCCCGCCTTCCTTCCTTCCTTCGCTCTCTCTCTCTCTCTCTCTCGCT
    ATCTTCTCAACGGAGACATGAAAGGCGTTTGTTAGGAAAAGAGGGGGGGGGGAAGAGTGGGACGACGCGC
    TGCGTCTTTTGGGCACTGGTCACGTGCGTCACCCTCTTTTTTTATCTCTATTGGCACTGTCTTGTTTCTT
    TTCCCTTTCCTATCATACGCGTCTCGCAAACGACTCCGCGCTGAGCAGCCATGTGCTGCGGCGTGGAGGA
    AGTACACAGACATCACGGATGCATATGTGCGCGTCCGTGTACGCGCTTGTATGGGGCTTCTAACAGCGCC
    TGTGTGTGTTTGTGTGTGTGTGTGTGTGTGTGTCTGTGTATTTCGAGCGTCTGTATGCTATTCTATTAAG
    CACCGAAGAAGAGACACACACGACAGCGAAGGAGATGGTGTCGGCTTTTCGGCTAATCACTCCCTTCCAT
    AGCTTCTCTGAAGGAGGCTCTCTTCCAGAGGAATAGACTGCAGATGGGGTCCACGTTTATCTGAGGAGTC
    AACGGAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAACTCGAG
  • Protein Sequence : Show Sequence
    >gi|1698880|gb|AAB37318.1| protein antigen LmSTI1 [Leishmania major]
    DATELKNKGNEEFSAGRYVEAVNYFSKAIQLDEQNSVLYSNRSACFAAMQKYKDALDDADKCISIKPNWA
    KGYVRRGAALHGMRRYDDAIAAYEKGLKVDPSNSGCAQGVKDVQVAKAREARDPIARVFTPEAFRKIQEN
    PKLSLLMLQPDYVKMVDTVIRDPSQGRLYMEDQRFALTLMYLSGMKIPNDGDGEEEERPSAKAAETAKPK
    EEKPLTDNEKEALALKEEGNKLYLSKKFEEALTKYQEAQVKDPNNTLYILNVSAVYFEQGDYDKCIAECE
    HGIEHGRENHCDYTIIAKLMTRNALCLQRQRKYEAAIDLYKRALVEWRNPDTLKKLTECEKEHQKAVEEA
    YIDPEIAKQKKDEGNQYFKEDKFPEAVAAYTEAIKRNPAEHTSYSNRAAAYIKLGAFNDALKDAEKCIEL
    KPDFVKGYARKGHAYFWTKQYNRALQAYDEGLKVDPSNADCKDGRYRTIMKIQEMASGQSADGDEAARRA
    MDDPEIAAIMQDSYMQLVLKEMQNDPTRIQEYMKDSGISSKINKLISAGIIRFGQ
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Researchers evaluated the potency of different DNA vaccine candidates in BALB/c mice using high dose footpad parasite challenge with L. major. Mice inoculated pCMV3ISS-LmSTI1 developed significantly smaller lesions in their footpads after challenge with the parasite. The vaccine was able to induce a partially protective effect (Ahmed et al., 2009).
  • Related Vaccine(s): L. major DNA Vaccine encoding LACKp24, TSA, LmSTI1 and CPa
8. PSA-2
  • Gene Name : PSA-2
  • Sequence Strain (Species/Organism) : Leishmania major
  • VO ID : VO_0011279
  • NCBI Protein GI : 1129058
  • Other Database IDs : CDD:165684
  • Taxonomy ID : 5664
  • Gene Strand (Orientation) : ?
  • Protein Name : surface antigen 2
  • Protein Length : 385
  • Protein Note : leucine-rich repeat receptor-like protein kinase; Provisional; PLN00113
  • Protein Sequence : Show Sequence
    >gi|1129058|gb|AAB38549.1| surface antigen 2 [Leishmania major]
    MAQCVRRLVLAATLAAAVALLLCTSSAPVARAAGTGDFTAAQRTNTLAVLQAFGRAIPKLGEKWAGNDFC
    SWEAVLCNAPDVYVSGISPTYAGTLPEMPVNVDYRHVVIKQLDFSEMGPGLSGTLPASWHSMTSLESLSI
    EKCESISGSVPPEWGSMTSLSVLNLRGTGISGTLPPQWSGMSKARSLQLQDCDLSGSLPSSWSAIPMLAS
    VSLKGNKFCGCVPDSWDQKAGLVVDIEDKHKGSDCLAAKDCTTTTTKPSATTATTPNLTNFPPTPRTTTE
    PLTTTSTEAPAEPTTTTEAPAEPTTTATPTNTPTPAPETECEVDGCEVCEGDSAARCARCREDYFLTDEK
    TCLKHNDGGVAAVSSGVAAAAVVCVAVLFSVGLAA
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Intraperitoneal vaccination of C3H/He mice with PSA-2 with Corynebacterium parvum as an adjuvant resulted in complete protection from lesion development after challenge infection with virulent L. major. Significant protection was also obtained in the genetically susceptible BALB/cH-2k and BALB/c mice (Handman et al., 1995).
  • Related Vaccine(s): L. major PSA-2 Protein Vaccine
9. SP
  • Gene Name : SP
  • Sequence Strain (Species/Organism) : Leishmania major
  • VO ID : VO_0011276
  • NCBI Protein GI : 23168331
  • Other Database IDs : CDD:31025
    CDD:119398
  • Taxonomy ID : 5664
  • Gene Strand (Orientation) : ?
  • Protein Name : signal peptidase type I
  • Protein Length : 180
  • Protein Note : Signal peptidase I [Intracellular trafficking and secretion]; COG0681
  • Protein Sequence : Show Sequence
    >gi|23168331|gb|AAN08877.1| signal peptidase type I [Leishmania major]
    MREHINTLLSLRVRDVIQQVVTVGLFLSIVLVGWRAVAVGTNCEASIVVVLSGSMEPGYYRGDVLLLHHR
    PEYPVTVGDIIVYTLPGQEIPIVHRVHRIHQRSEDGKKFYLTKGDNNVNDDRFLFRNGREWVEEGMIIGK
    TYAYVPRIGYLTIMFNESKIIKYLALGLIGFFLLTTTDEM
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : The potential protection of Lmjsp (Leishmania major signal peptidase) was evaluated in three different vaccination strategies (DNA/DNA, Protein/Protein and DNA/Protein), against L. major infection. We demonstrated that vaccination with SPase through all three mentioned strategies induced a parasite specific Th1 response and conferred partial protection against parasite challenge. However, our results indicated that DNA/DNA strategy developed more effective protective responses than the other two approaches and induced 81% reduction in L. major parasite load (Rafati et al., 2006).
  • Related Vaccine(s): L. major DNA Vaccine encoding SP
10. SW3.1
  • Gene Name : SW3.1
  • Sequence Strain (Species/Organism) : Leishmania major
  • VO ID : VO_0011280
  • NCBI Protein GI : 4008565
  • Other Database IDs : UniProtKB/TrEMBL: Q9TVI8
  • Taxonomy ID : 5664
  • Gene Strand (Orientation) : ?
  • Protein Name : histone H1
  • Protein Length : 105
  • Protein Sequence : Show Sequence
    >gi|4008565|emb|CAA11592.1| histone H1 [Leishmania major]
    MSSNSAAAAVSAATTSPQKSSRSSPKRAAVGKKTGAKKVAKKTGAKKVAKKPAKKVVKKPAKKVVKKPAK
    KVVKKAVKAVKKAVKKVVKAVKTAKKSSKKSSAKK
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : In a murine model of experimental cutaneous leishmaniasis, researchers investigated the protection elicited by injection of histone H1 (SW3.1) isolated from parasites by perchloric extraction, of a H1 recombinant protein produced in E. coli, and of H1 long and short synthetic peptides, against infection by L. major. Partial protection was achieved in most of the animals as shown by reduction in lesion size, upon immunization with histone H1 or its peptides, provided that the region 1-60 was present in the molecule (Solioz et al., 1999).
  • Related Vaccine(s): L. major H1 Protein Vaccine
11. TSA
  • Gene Name : TSA
  • Sequence Strain (Species/Organism) : Leishmania major
  • VO ID : VO_0011273
  • NCBI Nucleotide GI : 3411093
  • NCBI Protein GI : 3411094
  • Protein Accession : AAC31146.1
  • Other Database IDs : CDD:140280
    CDD:48564
  • Taxonomy ID : 5664
  • Gene Strand (Orientation) : ?
  • Protein Name : thiol specific antioxidant
  • Protein Length : 199
  • Protein Note : tryparedoxin peroxidase; Provisional; PTZ00253
  • DNA Sequence : Show Sequence
    >gi|3411093|gb|AF044679.1| Leishmania major thiol specific antioxidant (TSA) mRNA, complete cds
    CTGTACTTTATTGCCACCAGCCAGCCATGTCCTGCGGTAACGCCAAGATCAACTCTCCCGCGCCGTCCTT
    CGAGGAGGTGGCGCTCATGCCCAACGGCAGCTTCAAGAAGATCAGCCTCTCCTCCTACAAGGGCAAGTGG
    GTCGTGCTCTTCTTCTACCCGCTCGACTTTAGCTTCGTGTGCCCGACAGAGGTCATCGCGTTCTCCGACA
    GCGTGAGTCGCTTCAACGAGCTCAACTGCGAGGTCCTCGCGTGCTCGATAGACAGCGAGTACGCGCACCT
    GCAGTGGACGCTGCAGGACCGCAAGAAGGGCGGCCTCGGGACCATGGCGATCCCAATGCTAGCCGACAAG
    ACCAAGAGCATCGCTCGTTCCTACGGCGTGCTGGAGGAGAGCCAGGGCGTGGCCTACCGCGGTCTCTTCA
    TCATCGACCCCCATGGCATGCTGCGTCAGATCACCGTCAATGACATGCCGGTGGGCCGCAGCGTGGAGGA
    GGTTCTACGCCTGCTGGAGGCTTTTCAGTTCGTGGAGAAGCACGGCGAGGTGTGCCCCGCGAACTGGAAG
    AAGGGCGCCCCCACGATGAAGCCGGAACCGAATGCGTCTGTCGAAGGATACTTCAGCAAGCAGTAAACCT
    GTGAGCGTCGCAGGAGTCAGTGTGACCTCACCCGCCTCTGCCAGTGGGTGCGAGAGGGCGTGAGGGATTG
    TGGGAAGGCTGTTGGATATGATGCAGACAGCGATGAATGCAACTCCCACACACTGGCCCTCCTCAGCCCT
    CTCCACACAGACACACGCACGCATGTGCGGTGCTTCTGCTCCTTCATTTCCTGATGCGGTTTCTTTACTA
    TTTATGTTTTCCCCTGTTTTGGTTTCGCGGAATATGGACGCACGAACGCAGAGAGCAGAGGCGCGACACA
    CACACACGGGGCGCACACGTGTAAGCGACGGAGCGCGACACAGAGGGGAGAAGCCGGAAAGGATATATGA
    AATGAAGATGGTGTCCCGCACACACAGGCACGCACACGGGGCGAACGCGTGGCGCGTCCTTTCTATGGTT
    TCGCTGCTGCTGTTCGTGTTCTCGCTTCGCTGGTTGCAGTTCCGGCTCGTGCTGCCCTGCCTGCCACTCT
    TGGTCCGTGTCTGTCCGTGTCCGTGTCCGTGTGGGGGGGGGAGAGTTTTTCACTCCCCCGGTCACCTCTA
    CTGTTTATTATTTATATGTTTATTTATTTCCATATTGACTCAATTCATTCCGTGCGAAAGCCGGCTTGTT
    CCGGCGTCTTTTGACGAACAACTGCCCTATCAGCTGGTGATGGCCGTGTAGTGGACTGCCATGGCGTTGA
    CGGGAGCGGGGGATTAGGGTTCGATTCCGGAGAGGGAGCCTGAGAAATAGCTACCACTTCTACGGAGGGC
    AGCAGGCGCGCAAATTGCCCAATGTCAAAACAAAACGATGAGGCAGCGAAAAGAAATAGAGTTGTCAGTC
    CATTTGGATTGTCATTTCAATGGGGGATATTTAAACCCATCCAATATCGAGTAACAATTGGAGGACAAGT
    CTGGTGCCAGCACCCGCGGTAATTCCAGCTCCAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA
    AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA
    AAAAAAAAAAA
  • Protein Sequence : Show Sequence
    >gi|3411094|gb|AAC31146.1| thiol specific antioxidant [Leishmania major]
    MSCGNAKINSPAPSFEEVALMPNGSFKKISLSSYKGKWVVLFFYPLDFSFVCPTEVIAFSDSVSRFNELN
    CEVLACSIDSEYAHLQWTLQDRKKGGLGTMAIPMLADKTKSIARSYGVLEESQGVAYRGLFIIDPHGMLR
    QITVNDMPVGRSVEEVLRLLEAFQFVEKHGEVCPANWKKGAPTMKPEPNASVEGYFSKQ
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Researchers evaluated the potency of different DNA vaccine candidates in BALB/c mice using high dose footpad parasite challenge with L. major. Mice inoculated pCMV3ISS-TSA developed significantly smaller lesions in their footpads after challenge with the parasite. The vaccine was able to induce a partially protective effect (Ahmed et al., 2009).
  • Related Vaccine(s): L. major DNA Vaccine encoding LACKp24, TSA, LmSTI1 and CPa
III. Vaccine Information
1. L. major DNA Vaccine encoding Gp63
a. Vaccine Ontology ID:
VO_0004046
b. Type:
DNA vaccine
c. Status:
Research
d. Gene Engineering of Gp63
  • Type: DNA vaccine construction
  • Description:
  • Detailed Gene Information: Click here.
e. Vector:
pcDNA3 (Walker et al., 1998)
f. Immunization Route
Intradermal injection (i.d.)
g. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: Mice were injected intradermally in the ears, foot pads, dorsal skin, or hind leg muscles with 1-100 μg of plasmid DNA diluted in PBS, freeze-thawed parasites (1.6 X 105) in PBS, gp63 protein (10 μg) emulsified in Freund's complete adjuvant(FCA), in FCA or PBS alone in 50 to 70- μl volumes. All
    animals were boosted at 3 weeks (Walker et al., 1998).
  • Challenge Protocol: Promastigotes were subsequentiy resuspended in PBS (1 X 107 promastigotes/ml) and mice were infected by subcutaneous injection of 1 X 106 promastigotes (0.1 ml) in the dorsal side of the right foot 3 weeks after initial immunization (Walker et al., 1998).
  • Efficacy: gp63-pcDNA-3 vaccination protected 30% of susceptible mice (21 of 70) from Leishmania infection (Walker et al., 1998).
2. L. major DNA Vaccine encoding LACKp24, TSA, LmSTI1 and CPa
a. Vaccine Ontology ID:
VO_0004171
b. Type:
DNA vaccine
c. Status:
Research
d. Gene Engineering of TSA
  • Type: DNA vaccine construction
  • Description:
  • Detailed Gene Information: Click here.
e. Gene Engineering of Cpa
  • Type: DNA vaccine construction
  • Description:
  • Detailed Gene Information: Click here.
f. Gene Engineering of LmSTI1
  • Type: DNA vaccine construction
  • Description:
  • Detailed Gene Information: Click here.
g. Gene Engineering of LACK
  • Type: DNA vaccine construction
  • Description:
  • Detailed Gene Information: Click here.
h. Vector:
pCMV3ISS
i. Immunization Route
Intramuscular injection (i.m.)
j. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: For mice immunization, a single dose of 50 μg of Qiagen purified plasmid of each candidate DNA vaccine was administered intramusculary in 100 μl of PBS, 50 μl in each anterior tibialis muscle. Sham vaccination consisted of a single injection of 50 μg or 200 μg of Qiagen purified pCMV3ISS, the plasmid backbone, in the same conditions as immunized mice. A further control group of mice received no treatment at all (PBS). A group of mice was vaccinated with a cocktail of all 4 antigen carrying plasmids (pCMV3ISS-LACKp24, pCMV3ISS-TSA, pCMV3ISS-LmSTI1 and pCMV3ISS-CPa) (Ahmed et al., 2009).
  • Challenge Protocol: The appropriate number of promastigotes was inoculated subcutaneously in the right hind footpad of female BALB/c mice in 50 μl of PBS. The challenge of mice was carried out 2 weeks after the immunization (Ahmed et al., 2009).
  • Efficacy: A substantial increase of protection was achieved when the cocktail is composed of all of the four antigens; however, no full protection was achieved when mice were challenged with a high dose of parasite in their hind footpad. The full protection was only achieved after a challenge with a low parasitic dose in the dermis of the ear (Ahmed et al., 2009).
3. L. major DNA Vaccine encoding SP
a. Vaccine Ontology ID:
VO_0004172
b. Type:
DNA vaccine
c. Status:
Research
d. Gene Engineering of SP
  • Type: DNA vaccine construction
  • Description:
  • Detailed Gene Information: Click here.
e. Vector:
pcDNA3.1 (Rafati et al., 2006)
f. Immunization Route
Subcutanteous injection
g. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: Immunization experiments were carried out twice at 3 weeks intervals in five groups of 10 BALB/c mice. Mice in group I (DNA/DNA) were immunized subcutaneously (s.c.) in the right footpad with 100 μg of pcDNA-sp plasmid, in the both prime and boost vaccination. Two control groups (IV and V) were studied; mice in group IV (vector only/CpG) were inoculated using 100 μg of pcDNA (vector without insert) in the first vaccination and the same adjuvant regimen (50 μg CpG ODN and 70 (v/v) Montanide 720) in the second vaccination. Mice in group V (PBS) received PBS alone (Rafati et al., 2006).
  • Challenge Protocol: Animals were then challenged 3 weeks after completion of the immunization protocol with 3 × 105 L. major MRHO/IR/75/ER metacyclic promastigotes that had been suspended in 50 μl PBS and injected into the left footpad (Rafati et al., 2006).
  • Efficacy: DNA/DNA strategy developed more effective protective responses and induced 81% reduction in L. major parasite load (Rafati et al., 2006).
4. L. major DNA vaccine pcLACK + IL-22
a. Vaccine Ontology ID:
VO_0004530
b. Type:
DNA vaccine
c. Status:
Research
d. Host Species as Laboratory Animal Model:
Mouse
e. Gene Engineering of LACK
  • Type: DNA vaccine construction
  • Description:
  • Detailed Gene Information: Click here.
f. Vector:
pcDNA3 (Hezarjaribi et al., 2013)
g. Immunization Route
Intramuscular injection (i.m.)
h. Mouse Response
  • Vaccine Immune Response Type: VO_0000286
  • Immune Response: IL-22 obviously caused an increase in IFN-γ production and a decrease in IL-4 production before and after the challenge (p < 0.05) (Hezarjaribi et al., 2013).
  • Efficacy: Comparison of the mean size of lesions in the LACK and LACK + IL-22 groups demonstrated that the mean size of lesions of the two groups was significantly different from week four (p < 0.05). The survival rate at day 170 after challenge for the PBS, pcDNA3 (empty plasmid), pcLACK (pcDNA3 containing LACK gene), and pcLACK + IL-22 groups were 20%, 40%, 60%, and 80%, respectively (Hezarjaribi et al., 2013).
5. L. major H1 Protein Vaccine
a. Vaccine Ontology ID:
VO_0004176
b. Type:
Subunit vaccine
c. Status:
Research
d. Gene Engineering of SW3.1
e. Adjuvant: incomplete Freunds adjuvant
f. Immunization Route
Subcutaneous injection
g. Mouse Response
  • Host Strain: BALB/c, C57BL/6 or B10.D2
  • Vaccination Protocol: In all protection experiments, mice (n=5–8) were given injections (2×25 μl) of antigen preparation twice subcutaneously (s.c.) at the base of the tail. Before the injection, antigens were either emusified in IFA (1:1, vol/vol), mixed (1:1, vol/vol) with either 0.5 or 1 μg of IL-12 in PBS or prepared in PBS only. Several doses of antigen were tested and parasite challenge in the right hind footpad was performed at different time points after the second injection (Solioz et al., 1999).
  • Challenge Protocol: In this long term experiment, mice were challenged two and a half months after the second injection of antigen with 2×106 highly infectious parasites (Solioz et al., 1999).
  • Efficacy: When inoculated in the presence of IFA as adjuvant, the partially purified histone H1 was able to confer partial protection in six out of eight mice (Solioz et al., 1999).
6. L. major H2B Protein Vaccine
a. Vaccine Ontology ID:
VO_0004045
b. Type:
Subunit vaccine
c. Status:
Research
d. Antigen
The divergent amino-terminal region of H2B (Chenik et al., 2006).
e. Gene Engineering of H2B
  • Type: Recombinant protein preparation
  • Description:
  • Detailed Gene Information: Click here.
f. Adjuvant: CpG DNA vaccine adjuvant
g. Immunization Route
Subcutaneous injection
h. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: Three groups of mice were injected with 25 μg of either one of the three recombinant proteins (H2B, H2BΔN46 or H2BΔC65) with CpG. Three additional control groups received adjuvant (CpG or non-CpG) or PBS alone. Each mouse received two subcutaneous (s.c.) injections in the left footpad in a volume of 50 μl at 15 days intervals (Chenik et al., 2006).
  • Challenge Protocol: Four weeks after the second dose, mice were infected in the right footpad with 2 × 106 L. major metacyclic promastigotes, in 50 μl of PBS (Chenik et al., 2006).
  • Efficacy: The divergent amino-terminal region of H2B is able to confer potent protection against a virulent challenge in BALB/c mice. Mice immunized with the amino-terminal part of H2B in presence of CpG are more resistant than those immunized, in the same conditions, by the whole protein (p < 0.05, from week 5) after L. major challenge (Chenik et al., 2006).
7. L. major PSA-2 Protein Vaccine
a. Vaccine Ontology ID:
VO_0004044
b. Type:
Subunit vaccine
c. Status:
Research
d. Gene Engineering of PSA-2
  • Type: Recombinant protein preparation
  • Description:
  • Detailed Gene Information: Click here.
e. Adjuvant: killed Corynebacterium parvum vaccine adjuvant
f. Immunization Route
Intraperitoneal injection (i.p.)
g. Mouse Response
  • Host Strain: C3H/He and BALB/c H-2^k
  • Vaccination Protocol: Groups of 8 to 16 mice were injected three times, every 2 weeks, intraperitoneally with 1.5 to 2 mg of purified PSA-2mixed with 200 mg of killed Corynebacterium parvum as an adjuvant (Handman et al., 1995).
  • Challenge Protocol: Two weeks after the last injection, all mice were bled individually and divided into groups; one group was used to examine T-cell responses to PSA-2 antigen, and another group was challenged with 105 live promastigotes.
  • Efficacy: Intraperitoneal vaccination of C3H/He mice with PSA-2 with Corynebacterium parvum as an adjuvant resulted in complete protection from lesion development after challenge infection with virulent L. major. Significant protection was also obtained in the genetically susceptible BALB/cH-2k and BALB/c mice (Handman et al., 1995).
8. L. T -PpSP15
a. Vaccine Ontology ID:
VO_0004627
b. Type:
Recombinant vector vaccine
c. Status:
Research
d. Host Species for Licensed Use:
Human
e. Vector:
(Zahedifard et al., 2014)
f. Immunization Route
Intramuscular injection (i.m.)
g. Mouse Response
  • Vaccine Immune Response Type: VO_0003057
  • Efficacy: In both susceptible BALB/c and resistant C57BL/6 mice, the strongest protective effect was observed when priming with PpSP15 DNA and boosting with PpSP15 DNA and live recombinant L. tarentolae stably expressing cysteine proteinase genes (Zahedifard et al., 2014).
9. Leishmania major DNA vaccine KMP-11
a. Vaccine Ontology ID:
VO_0004373
b. Type:
DNA vaccine
c. Status:
Research
d. Host Species as Laboratory Animal Model:
Mouse
e. Gene Engineering of KMP-11
  • Type: DNA vaccine construction
  • Description: Since this vaccine was cross-protective, the KMP-11 gene was from L. donovani (Bhaumik et al., 2009).
  • Detailed Gene Information: Click here.
f. Vector:
pCMV-LIC
g. Immunization Route
Intramuscular injection (i.m.)
h. Mouse Response
  • Vaccine Immune Response Type: VO_0000286
  • Efficacy: Lesion size of the LM infected groups immunized additionally with IL-12 showed significant reduction at 12 weeks post-infection compared to mice immunized with KMP-11 DNA alone (p < 0.05). Moreover, we examined the parasite loads in the local draining lymph nodes which showed ∼96.2% and 94% reduction in parasite burden in groups of immunized mice treated additionally with (IL-12p35 + IL-12p40) DNA or rmIL-12, respectively (p < 0.05). KMP-11 DNA immunized mice showed 69% reduction in LM-load in draining lymph node suggesting KMP-11 DNA immunization alone was partially protective against LM (Bhaumik et al., 2009).
10. SL3261-L. major
a. Vaccine Ontology ID:
VO_0004671
b. Type:
Recombinant vector vaccine
c. Status:
Research
d. Host Species for Licensed Use:
Baboon
e. Gene Engineering of KMP-11
  • Type: Recombinant protein preparation
  • Description: Antigens were differentially expressed on the surface or in the cytosol of Salmonella typhimurium SL3261 (Schroeder et al., 2011).
  • Detailed Gene Information: Click here.
f. Preparation
Salmonella expressing the novel Leishmania antigens LinJ08.1190 and LinJ23.0410 (Schroeder et al., 2011)
g. Immunization Route
Intramuscular injection (i.m.)
h. Mouse Response
  • Vaccination Protocol: Mice were vaccinated with a single dose of Salmonella vaccine strains, the carrier control SL3261 or treated with PBS (Schroeder et al., 2011).
  • Vaccine Immune Response Type: VO_0000287
  • Challenge Protocol: Mice were subsequently challenged with 2×106 late-stationary phase L. major promastigotes into the left hind footpad (Schroeder et al., 2011).
  • Efficacy: We show that 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 (Schroeder et al., 2011).
IV. References
1. Ahmed et al., 2009: Ahmed SB, Touihri L, Chtourou Y, Dellagi K, Bahloul C. DNA based vaccination with a cocktail of plasmids encoding immunodominant Leishmania (Leishmania) major antigens confers full protection in BALB/c mice. Vaccine. 2009; 27(1); 99-9106. [PubMed: 18951941].
2. Ameen, 2010: Ameen M. Cutaneous leishmaniasis: advances in disease pathogenesis, diagnostics and therapeutics. Clinical and experimental dermatology. 2010; 35(7); 699-705. [PubMed: 20831602].
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. Chenik et al., 2006: Chenik M, Louzir H, Ksontini H, Dilou A, Abdmouleh I, Dellagi K. Vaccination with the divergent portion of the protein histone H2B of Leishmania protects susceptible BALB/c mice against a virulent challenge with Leishmania major. Vaccine. 2006; 24(14); 2521-2529. [PubMed: 16417957].
5. Handman et al., 1995: Handman E, Symons FM, Baldwin TM, Curtis JM, Scheerlinck JP. Protective vaccination with promastigote surface antigen 2 from Leishmania major is mediated by a TH1 type of immune response. Infection and immunity. 1995; 63(11); 4261-4267. [PubMed: 7591056].
6. Hezarjaribi et al., 2013: Hezarjaribi HZ, Ghaffarifar F, Dalimi A, Sharifi Z, Jorjani O. Effect of IL-22 on DNA vaccine encoding LACK gene of Leishmania major in BALB/c mice. Experimental parasitology. 2013; 134(3); 341-348. [PubMed: 23541883].
7. Rafati et al., 2002: Rafati S, Kariminia A, Seyde-Eslami S, Narimani M, Taheri T, Lebbatard M. Recombinant cysteine proteinases-based vaccines against Leishmania major in BALB/c mice: the partial protection relies on interferon gamma producing CD8(+) T lymphocyte activation. Vaccine. 2002; 20(19-20); 2439-2447. [PubMed: 12057598].
8. Rafati et al., 2006: Rafati S, Ghaemimanesh F, Zahedifard F. Comparison of potential protection induced by three vaccination strategies (DNA/DNA, Protein/Protein and DNA/Protein) against Leishmania major infection using Signal Peptidase type I in BALB/c mice. Vaccine. 2006; 24(16); 3290-3297. [PubMed: 16481076].
9. Reithinger et al., 2007: Reithinger R, Dujardin JC, Louzir H, Pirmez C, Alexander B, Brooker S. Cutaneous leishmaniasis. The Lancet infectious diseases. 2007; 7(9); 581-596. [PubMed: 17714672].
10. 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].
11. Solioz et al., 1999: Solioz N, Blum-Tirouvanziam U, Jacquet R, Rafati S, Corradin G, Mauël J, Fasel N. The protective capacities of histone H1 against experimental murine cutaneous leishmaniasis. Vaccine. 1999; 18(9-10); 850-859. [PubMed: 10580198].
12. Walker et al., 1998: Walker PS, Scharton-Kersten T, Rowton ED, Hengge U, Bouloc A, Udey MC, Vogel JC. Genetic immunization with glycoprotein 63 cDNA results in a helper T cell type 1 immune response and protection in a murine model of leishmaniasis. Human gene therapy. 1998; 9(13); 1899-1907. [PubMed: 9741428].
13. Zahedifard et al., 2014: Zahedifard F, Gholami E, Taheri T, Taslimi Y, Doustdari F, Seyed N, Torkashvand F, Meneses C, Papadopoulou B, Kamhawi S, Valenzuela JG, Rafati S. Enhanced protective efficacy of nonpathogenic recombinant leishmania tarentolae expressing cysteine proteinases combined with a sand fly salivary antigen. PLoS neglected tropical diseases. 2014; 8(3); e2751. [PubMed: 24675711].