VIOLIN: Vaccine Investigation and Online Information Network

Leishmania major

Table of Contents

General Information
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. LeIF (Protective antigen)
8. LmSTI1 (Protective antigen)
9. PEPCK (Protective antigen)
10. PSA-2 (Protective antigen)
11. ribosomal protein L3 (Protective antigen)
12. ribosomal protein L5 (Protective antigen)
13. SP (Protective antigen)
14. SW3.1 (Protective antigen)
15. TSA (Protective antigen)
Vaccine Information
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).

II. Vaccine Related Pathogen Genes

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:185513
CDD:285458
CDD:278538
CDD:239068
Taxonomy ID : 5664
Gene Strand (Orientation) : ?
Protein Name : cysteine protease
Protein pI : 6.62
Protein Weight : 33970.17
Protein Length : 391
Protein Note : cathepsin L protease; Provisional

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

>AAZ23598.1 cysteine protease, partial [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:278538
CDD:239068
GOA:Q5ZQK2
InterPro: IPR000169
InterPro: IPR000668
InterPro: IPR013128
UniProtKB/TrEMBL: Q5ZQK2
Taxonomy ID : 5664
Gene Strand (Orientation) : ?
Protein Name : cysteine proteinase b
Protein pI : 4.28
Protein Weight : 17436.69
Protein Length : 240
Protein Note : Papain family cysteine protease; pfam00112

Protein Sequence : Show Sequence

>CAD54749.1 cysteine proteinase b, partial [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:279761
Taxonomy ID : 5664
Gene Strand (Orientation) : ?
Protein Name : GP63
Protein pI : 6.66
Protein Weight : 58512.43
Protein Length : 648
Protein Note : Leishmanolysin; pfam01457

Protein Sequence : Show Sequence

>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:304987
Taxonomy ID : 5664
Gene Strand (Orientation) : ?
Protein Name : histone H2B
Protein pI : 11.84
Protein Weight : 11691.58
Protein Length : 157
Protein Note : Histone H2B; cl23830

Protein Sequence : Show Sequence

>AAK21263.1 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:281087
Taxonomy ID : 5661
Gene Strand (Orientation) : ?
Protein Name : Kinetoplastid membrane protein 11
Protein pI : 7.89
Protein Weight : 14076.21
Protein Length : 246
Protein Note : KMP-11; Lipophosphoglycan-associated protein; LPGAP

Protein Sequence : Show Sequence

>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): L. major DNA vaccine encoding TSA, LMSTI1, KMP11, and LACK , 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:238121
CDD:225201
CDD:293791
Taxonomy ID : 5664
Gene Strand (Orientation) : ?
Protein Name : LACK
Protein pI : 6.64
Protein Weight : 32575.5
Protein Length : 354
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 from...; 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

>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 encoding TSA, LMSTI1, KMP11, and LACK , L. major DNA vaccine pcLACK + IL-22

7. LeIF

Gene Name : LeIF
Sequence Strain (Species/Organism) : Leishmania major strain Friedlin
NCBI Gene ID : 12981542
NCBI Protein GI : 389592667
Locus Tag : LMJF_03_0980
Genbank Accession : FR796399
Protein Accession : XP_003721774
Taxonomy ID : 347515
Chromosome No : 3
Gene Starting Position : 381259
Gene Ending Position : 382557
Gene Strand (Orientation) : -
Protein pI : 5.61
Protein Weight : 45612.68
Protein Length : 432

DNA Sequence : Show Sequence

>NC_004916.2:381259-382557 Leishmania major strain Friedlin complete genome, chromosome 3
ATTAGTCCGCATCCTCATCATCATCGTCTTCCCCATCAAAGCCCTTCTTGCCCTCGTCTGCGTCGCCGTG
AGGCTGCGGAGGCGACACCACCTTCAGCTGGCCACCGCGCTTCTTGATTTCCGCCGTCATTGCCTCTATT
GCCTCCTTCATTCGCTGAATACCCTCTTCCTTCATATCCGTGCGCGCGCGGATGCCGTACTTGGGGGGTC
CGATGATGTTGACGGAGAGGTGGATCTGAGGATCGCTGCCTTCGCCGTAGCTGCGGCCCAGAATGAGGAC
GTCGCGGATCGCCTCCACACCATCACACGCGAAGCACGTGATCTCGACTTCCGCGAACAGCGTCAACACC
TTCAGCCGCATCGCGTTCTTCAGCGTCAGCATCAGGCAATCCGATATAGCCTTTTCAAGCTTCAGCGGAC
CAAGAATACGCTCCACATCTTCCGTCTGGTTCAGTTCGTAAAGCCACGTCCACGCGTGTTTGCCCGGTTC
CCGCTGGTAGAGCGGATAGGCGATCATTTCCATCGCATCCATAGCGGGGATATCACACAGCTCAGCGACA
TGGCAAACAATGGAGCGAACTTCGTTACCCTGGCGGAAGTGCGCTTCGCACGCCTTTGCTTCGTTGGGCG
TTACCAGCTTCTTTGACAAGTCAATGTAACCCTTGTCCTTGTCGATACGGATCACCTGCGCGGGCTCAGT
GCGGCCTACCTTGATTAGCTTTCCCATCGAGCGCACACGGCGTCTAGTCACCTCCGTGTACGGAATAATG
CCTTCCCGCTTGCCGTACTCGAGCAGCTGCACTACCGCGGAGGTGTCATTCACCTGGGTGATTTTTACCC
ACACGACGTCGTTGATCTTCGGCATCGTTTCAACGTAGAACGGAATGTCCTTGCCATCCCATGAGGTAAT
GCCCAGGCACCCACAGACAAACTTCTGCTGGCGCTTGTTCAGGTCACGCATCCACTCTGGACGCTCGTTA
TTGCTACCCTTCGTCTCACCCTCCACAACCTGCGCGGAGAGAATTGTGGCCTTCTCAAGAAGCACCAGCA
AGTGGTCCAGCGTTCTGCAGTCAACTGGAACCGGGAACGGCTCCGCTAATAGGAGCTTTCGCCGCGCCAA
GCTCTGATTGAGGCGGAAGTACTCTTTTGGAACGGCATAGTAGACATTGTCCGTCGTTCGGCAGCAGCAC
TTCGTTTTGTAGTCCACAGTTTCGGGACTATCGGTGACACAGTAAGAAGCCATGCTTTCGTTGTTGCAAA
ATATAATTCTTTCGAGGGGGCGGCACAGGGATACCCACA

Protein Sequence : Show Sequence

>XP_003721774.1 putative elongation initiation factor 2 alpha subunit [Leishmania major strain Friedlin]
MWVSLCRPLERIIFCNNESMASYCVTDSPETVDYKTKCCCRTTDNVYYAVPKEYFRLNQSLARRKLLLAE
PFPVPVDCRTLDHLLVLLEKATILSAQVVEGETKGSNNERPEWMRDLNKRQQKFVCGCLGITSWDGKDIP
FYVETMPKINDVVWVKITQVNDTSAVVQLLEYGKREGIIPYTEVTRRRVRSMGKLIKVGRTEPAQVIRID
KDKGYIDLSKKLVTPNEAKACEAHFRQGNEVRSIVCHVAELCDIPAMDAMEMIAYPLYQREPGKHAWTWL
YELNQTEDVERILGPLKLEKAISDCLMLTLKNAMRLKVLTLFAEVEITCFACDGVEAIRDVLILGRSYGE
GSDPQIHLSVNIIGPPKYGIRARTDMKEEGIQRMKEAIEAMTAEIKKRGGQLKVVSPPQPHGDADEGKKG
FDGEDDDDEDAD

Molecule Role : Protective antigen
Related Vaccine(s): LEISH-F1+MPL-SE

8. 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:290150
CDD:278916
CDD:276809
CDD:290160
CDD:128966
Taxonomy ID : 5664
Gene Strand (Orientation) : ?
Protein Name : protein antigen LmSTI1
Protein pI : 6.04
Protein Weight : 60559.91
Protein Length : 617
Protein Note : TPR repeat; pfam13414

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

>AAB37318.1 protein antigen LmSTI1, partial [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 , L. major DNA vaccine encoding TSA, LMSTI1, KMP11, and LACK , LEISH-F1+MPL-SE

9. PEPCK

Gene Name : PEPCK
Sequence Strain (Species/Organism) : Leishmania major strain Friedlin
NCBI Gene ID : 5649768
NCBI Protein GI : 157865574
Locus Tag : LMJF_11_0260
Genbank Accession : FR796407
Protein Accession : XP_001681494
Taxonomy ID : 347515
Chromosome No : 11
Gene Starting Position : 69920
Gene Ending Position : 71704
Gene Strand (Orientation) : +
Protein pI : 9.59
Protein Weight : 62249.18
Protein Length : 594

DNA Sequence : Show Sequence

>NC_007252.2:69920-71704 Leishmania major strain Friedlin complete genome, chromosome 11
GATGATGCGTCTTTCTCGGCTTGGCGTCACGGCCGCCGCCGCCGCGCCGTCGTCGTTTCCGCTGCTTCAG
CAGCTCCGTGGCGTGCGCTACGCCAACATCCAGGAGACTCTGAAGCCCATCCCTGGTCAAACTGCAGGCC
AGATCTCCATCTTGAACGAGATATGCTGCAACCCGGATGCGGAGGAGGAGCGACGCAAGCCCGTCTTCCG
TGCTGAGGTGATGCCAGATGCGGCCGCCGCGGCAGAGGAGGACAACTACCTGCACACGATGCACAAGTGG
GGCTACGACTCGCTGACGCTCTTCAAGAAGACGAACGAAGACCCTGGGCCGTGGTGGAACGCCAACGCCA
GCACGCTGGCGTCTAACTGGTCGCAGGTTGGCGATTACGCGAATGCCGGCATGTGGTCGGGCGTGTGGCG
CTACACGTACGGCATCGGCGAGTATAACCTGCGCCCTTACGAGCTGCGTGGACGTGCGTGGGGCCGCAAG
GACCCCAAGACCGGCGCCGTCATGATCCGCTACGGCAAGCGCAGCACCAGCAAGCCGGTGCAGAGGCTCT
GCTTTCCGCACACGAAGGAGCACGAGCAGCATCACCGTATCAAAAACCCGGCAAACAAGGACGTGAAGGA
GATCTCAGCCCTGCACGGCAAGCGCATTCTGCGCGAGCTTCAGTACCACCTCGGTCAAGGGCTGCGTTTC
TACCTGGTAGACGGCGTCTTTGGGAGCGACCCAGGCACCGCTACCCCGTACCGCATCATCACGGACACCC
CGACGCATGCCTACTTTGCGTCCATGGCAGCGATTCGCACCTTCAACTACGTGGCGCGGCAGGAGGTGAC
GCTTGTGAAGCGACTGTCGCAGTCGCCGATCGACGAGTGGGGGTGGCGCCGTCCTGGCGTGCTCATCTAC
CACGCCCCCTCCTACGACTTTGAGAGCCCGCGCATCGTCGAGGAGTTTGGCGGGCCGCGTCCGAAGGATA
TGGGGCTCAGTCACAACCGCTTCATCGCAACAGAGCCTTACAGCATTCCCATGAAGTGCGCCATGGGTGG
CGAGCCCAGCTGCGACGCACTCCTCGACAGCACAGCGATGCTGTGCGGTCGCTGGGGATTCTACGCCGAC
GAGAAAGGCTACCTCACCGTCCCTGGCGAGTCGATCATGTCGAAGGATGGGCGCTCGCTGACGCTGGTGA
TCACCGGCGACGAGGCCGACGCGGACGCTCTGCGCACGTCGCCGCAGCTCTACGGTAGCCGACATCACCG
CATCGCCAACGGCGTTGTATCCCGTGCGTGGGATGTCGTCTCGATGCCGGCGTGCGCCACTGGCGCAAAG
CCGCTGCCCACCGACATAGTGGAGCAGGACCTGCAGCGGGTGCAGCGCAGCTTGCCCACGCGCATGGGCC
TCCCGCATACCCTCTCACACCGCCACCACGGCCGCCGCCACGTCAGCGAGTACGGCTTCAAGTGGCCACA
CAACTACACGGAGGATGTTTCCACGAAGGCGTACGCCGGTGGGCATCTGTTCAAGGCGCCGAAGACCGAC
AAGCTCGCCGGCCATCAGCCGCGTCCTTCGAGGTTTTTGATGAAGGATGTCGATGTGGTGGTCATTGGCG
AGGGAGTCGACGCCGCCGCGGCTGTTGTAAGCACACTCAAGGACCGCGGCATGTTGTACGCCGAAGAGGC
GCCGCTGAAGGAGGCGATGGCGACGGCGCTGAAGGCGGCAAAGAGTGTAAAAGTGGTGCCCCGTGCAAGC
TCGAAGGTCGTGCTAGGGAAGCTGACGCATGTGTA

Protein Sequence : Show Sequence

>XP_001681494.1 conserved hypothetical protein [Leishmania major strain Friedlin]
MMRLSRLGVTAAAAAPSSFPLLQQLRGVRYANIQETLKPIPGQTAGQISILNEICCNPDAEEERRKPVFR
AEVMPDAAAAAEEDNYLHTMHKWGYDSLTLFKKTNEDPGPWWNANASTLASNWSQVGDYANAGMWSGVWR
YTYGIGEYNLRPYELRGRAWGRKDPKTGAVMIRYGKRSTSKPVQRLCFPHTKEHEQHHRIKNPANKDVKE
ISALHGKRILRELQYHLGQGLRFYLVDGVFGSDPGTATPYRIITDTPTHAYFASMAAIRTFNYVARQEVT
LVKRLSQSPIDEWGWRRPGVLIYHAPSYDFESPRIVEEFGGPRPKDMGLSHNRFIATEPYSIPMKCAMGG
EPSCDALLDSTAMLCGRWGFYADEKGYLTVPGESIMSKDGRSLTLVITGDEADADALRTSPQLYGSRHHR
IANGVVSRAWDVVSMPACATGAKPLPTDIVEQDLQRVQRSLPTRMGLPHTLSHRHHGRRHVSEYGFKWPH
NYTEDVSTKAYAGGHLFKAPKTDKLAGHQPRPSRFLMKDVDVVVIGEGVDAAAAVVSTLKDRGMLYAEEA
PLKEAMATALKAAKSVKVVPRASSKVVLGKLTHV

Molecule Role : Protective antigen
Related Vaccine(s): L. major synthetic DNA vaccine IDM2

10. PSA-2

Gene Name : PSA-2
Sequence Strain (Species/Organism) : Leishmania major
VO ID : VO_0011279
NCBI Protein GI : 1129058
Other Database IDs : CDD:215061
CDD:275380
Taxonomy ID : 5664
Gene Strand (Orientation) : ?
Protein Name : surface antigen 2
Protein pI : 4.54
Protein Weight : 37463.69
Protein Length : 441
Protein Note : leucine-rich repeat receptor-like protein kinase; Provisional

Protein Sequence : Show Sequence

>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

11. ribosomal protein L3

Gene Name : ribosomal protein L3
Sequence Strain (Species/Organism) : Leishmania major
NCBI Protein GI : AAY51372
Other Database IDs : CDD:240267
CDD:294230
Taxonomy ID : 5664
Protein Name : ribosomal protein L3
Protein pI : 11.62
Protein Weight : 43952
Protein Length : 478
Protein Note : 60S ribosomal protein L3; Provisional

Protein Sequence : Show Sequence

>AAY51372.1 ribosomal protein L3 [Leishmania major]
MSHCKFEHPRHGHLGFLPRKRSRQIRGRARAFPKDDATQKPHLTSFMVFKAGMTHIVRDVDRPGSKVNKK
EVVEPVTILEAPPMVIVGIVGYRQTPVGLKTIGTVWAHHTSVEFRRRYYKNWKQSAQLAFSRQKQFANTK
EGKVAEARTLNAFAKKASVIRVIAHTQLRKLRNHRVGVKKAHVQEIQVNGGSVAAKIALAKSLLEKEVRV
DSVFQQSEACDVCSVTKGHGTEGVVKRWGVACLPRKTHRGLRKVACIGAWHPARVMYTVARAGQHGYHHR
TQLNKKIYQIGRSVAVEPNQATTTYDLTAKTITPMGGFVGYGTVRNDYVMLKGSVSGPRRRVMTLRRPMA
PQTSRQLKEKIVLKFIDTSSKIGHGRFQTKKEKNQWFGPLKKDRIRREERLRKERAARAVERKAKAAKK

Molecule Role : Protective antigen
Molecule Role Annotation : (Ramirez et al., 2014)

12. ribosomal protein L5

Gene Name : ribosomal protein L5
Sequence Strain (Species/Organism) : Leishmania major
NCBI Protein GI : XP_003722581
Other Database IDs : CDD:240254
CDD:279233
CDD:238246
CDD:290906
GOA:E9AF09
InterPro: IPR005484
InterPro: IPR005485
InterPro: IPR025607
UniProtKB/TrEMBL: E9AF09
Taxonomy ID : 347515
Gene Strand (Orientation) : ?
Protein Name : putative 60S ribosomal protein L5
Protein pI : 10.69
Protein Weight : 32276.822
Protein Length : 396
Protein Note : 60S ribosomal protein L5; Provisional

Protein Sequence : Show Sequence

>XP_003722581.1 putative 60S ribosomal protein L5 [Leishmania major strain Friedlin]
MPFVKVVKNKAYFKRFQVKYRRRREGKTDYHARRQMVLQDKTKFGSPKYRLVVRITNKDIIAQIVQAKIV
GDEVVMAAYAHELPAFGIEHGLTNYAAAYATGLLLARRTLAKLGIADKFQGAKEADGSYSAVRTKKDDEG
DDEERFPFKAILDVGLARTTTGARVFGVLKGAVDGGMAVPHRPNRFPGYNKEKSSLDAKVHRDRIFGKHV
ADYLKQVKEEASSNPDEKCVQFSKYMAAKVLPESIEGMYKKAHAAIRADPSKSLPKKAKKEGVAHKSYKT
KKLSGAEKRAAAKAKVAAIRERLGK

Molecule Role : Protective antigen
Molecule Role Annotation : (Ramirez et al., 2014)

13. SP

Gene Name : SP
Sequence Strain (Species/Organism) : Leishmania major
VO ID : VO_0011276
NCBI Protein GI : 23168331
Other Database IDs : CDD:299172
CDD:119398
Taxonomy ID : 5664
Gene Strand (Orientation) : ?
Protein Name : signal peptidase type I
Protein pI : 7.75
Protein Weight : 18937.49
Protein Length : 239
Protein Note : The S24, S26 LexA/signal peptidase superfamily contains LexA-related and type I signal peptidase families. The S24 LexA protein domains include: the lambda repressor CI/C2 family and related bacterial prophage repressor proteins; LexA (EC 3.4.21.88), the...; cl10465

Protein Sequence : Show Sequence

>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

14. 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 pI : 12.41
Protein Weight : 9728.18
Protein Length : 150

Protein Sequence : Show Sequence

>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

15. 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:239313
Taxonomy ID : 5664
Gene Strand (Orientation) : ?
Protein Name : thiol specific antioxidant
Protein pI : 6.75
Protein Weight : 20885.27
Protein Length : 261
Protein Note : tryparedoxin peroxidase; Provisional

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

>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 , L. major DNA vaccine encoding TSA, LMSTI1, KMP11, and LACK , LEISH-F1+MPL-SE

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 encoding TSA, LMSTI1, KMP11, and LACK

a. Type:

DNA vaccine

b. Status:

Research

c. Host Species for Licensed Use:

Human

d. Gene Engineering of KMP-11

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

e. Gene Engineering of TSA

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

f. Gene Engineering of LACK

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

g. Gene Engineering of LmSTI1

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

h. Adjuvant: IL-12 vacince adjuvant

VO ID: VO_0001147

i. Vector:

pEGFP-N1(Salehi-Sangani et al., 2019)

j. Immunization Route

Intramuscular injection (i.m.)

k. Mouse Response

Host Strain: BALB/c
Vaccination Protocol: BALB/c mice were divided into four groups (9 mice per group), one group was injected with 100 µg pleish-dom alone, one group was injected with pleish-dom combined with plasmid encoding IL-12 (50 µg+50 µg, pIL-12), another group received PBS, and one group received 100 µg empty pcDNA intramuscularly in the hind leg. The booster injections were given three times in 2-week intervals.(Salehi-Sangani et al., 2019)
Immune Response Assay Type: Enzyme-linked immunosorbent assay (ELISA)
Challenge Protocol: Four weeks after the last booster injection, different groups of mice were challenged subcutaneously at the base of the tail with 1×106 L. major promastigotes harvested at stationary phase. Lesion development was monitored, and the size of the lesion was recorded weekly using a Vernier caliper.(Salehi-Sangani et al., 2019)

5. 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).

6. L. major H1 Protein Vaccine

a. Vaccine Ontology ID:

VO_0004176

b. Type:

Subunit vaccine

c. Status:

Research

d. Gene Engineering of SW3.1

Type: Recombinant protein preparation
Description: Recombinant H1 protein (Solioz et al., 1999)
Detailed Gene Information: Click here.

e. Adjuvant: incomplete Freunds adjuvant

VO ID: VO_0000142

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).

7. 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

VO ID: VO_0001237

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).

8. 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

VO ID: VO_0001259

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).

9. L. major synthetic DNA vaccine IDM2

a. Type:

DNA vaccine

b. Status:

Research

c. Host Species for Licensed Use:

Human

d. Antigen

PEPCK - dominant naturally processed peptide that elicits strong CD4(+) T cell responses in infected mice and humans(Mou et al., 2015)

e. Gene Engineering of PEPCK

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

f. Immunization Route

Intradermal injection (i.d.)

g. Mouse Response

Host Strain: C57BL/6
Vaccination Protocol: Performed intramuscular DNA delivery of either IDM2 or PB in C57BL/6 mice at a dose of 20 μg each, followed by EP, two times, 2 weeks apart(Louis et al., 2019)
Immune Response: Both mice vaccinated with IDM2 and those vaccinated with PB mounted a robust immune response, with avereages of 2500 SFU/million and 3700 SFU/million splenocytes against IDM2 and PB, respectively. A greater number of CD4+ T cells responded to peptides in pool 1 of PB than in pool 1 of IDM2.(Louis et al., 2019)
Immune Response Assay Type: Enzyme-linked immunosorbent spot (ELISpot) assay
Challenge Protocol: Immunized mice twice, at a 2 week interval, by either i.m. or i.d. EP. flank or TA skin from vaccination and contralateral sites was harvested spleens 45 days after the final vaccination.

10. 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).

11. LEISH-F1+MPL-SE

a. Type:

Subunit vaccine

b. Status:

Clinical trial

c. Host Species for Licensed Use:

Human

d. Antigen

LEISH-F1: a polyprotein composed of these three priority candidate antigens (LmSTI1, TSA, LeIF) fused in tandem, Leish-111f(Coler et al., 2002)

e. Adjuvant: MPL-SE vaccine adjuvant

VO ID: VO_0001345

f. Immunization Route

subcutaneous injection

g. Human Response

Vaccination Protocol: a randomized, double-blind, controlled, dose-escalating clinical trial and were randomly assigned to receive three injections of either the LEISH-F1+MPL-SE vaccine (consisting of 5, 10, or 20 μg recombinant Leishmania polyprotein LEISH-F1 antigen+25 μg MPL-SE adjuvant) (n=27), adjuvant alone (n=8), or saline placebo (n=9). The study injections were given subcutaneously on Days 0, 28, and 56, and the patients were followed through Day 336 for safety, immunological, and clinical evolution endpoints. (Nascimento et al., 2010)
Immune Response: IgG antibody response to LEISH-F1 in all vaccine recipients, no significant differences in titer among vaccine recipients who received 5, 10, or 20 μg of LEISH-F1 + 25 μg MPL-SE(Nascimento et al., 2010)
Side Effects: does not induce many AE's (mild or moderate headache and fever in few recipients)(Nascimento et al., 2010)

12. 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).

13. 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. Ramirez et al., 2014: Ramirez L, Corvo L, Duarte MC, Ch�vez-Fumagalli MA, Valadares DG, Santos DM, de Oliveira CI, Escutia MR, Alonso C, Bonay P, Tavares CA, Coelho EA, Soto M. Cross-protective effect of a combined L5 plus L3 Leishmania major ribosomal protein based vaccine combined with a Th1 adjuvant in murine cutaneous and visceral leishmaniasis. Parasites & vectors. 2014; 7; 3. [PubMed: 24382098].

10. 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].

11. 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].

12. 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].

13. 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].

14. 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].