Immunogenicity of HLA-DR1 Restricted Peptides Derived from Leishmania major gp63 Using FVB/N-DR1 Transgenic Mouse Model
Abstract
Background: Leishmaniasis is a worldwide disease prevalent in tropical and sub- tropical countries. In the present study the immunogenicity of three human HLA-DR1 restricted peptides derived from L. major gp63 protein was evaluated using FVB/N-DR1 transgenic mouse model.
Methods: The immunity generated by three MHC class II – restricted peptides with the sequence of AARLVRLAAAGAAVT (AAR), AAPLVRLAAAGAAVT (AAP) and SRYDQLVTRVVTHE (ASR) derived from L. major gp63 protein were predicted using a web-based software (SYFPEITHI) and tested in FVB/N-DR1 transgenic mice.
Results: Immunization of FVB/N-DR1 transgenic mice with one of the three predicted peptides (AAR) resulted in high levels of Th1-type immune response as well as significant levels of IFN-γ de-tected by Proliferation assay and ELISA.
Conclusion: The results indicate a high level of immunogenicity for AAR, which can be a potent candidate for peptide vaccine in Leishmania infections.
Royer MA, Crowe CO. American cutaneous Leishmaniasis. Arch Pathol Lab Med. 2002; 126(4):471-473.
Leishmaniasis; Strategic direction for research available from: [http://www.who.int/ leish/direction.htm].
Griekspoor A, Sondorp E, Vos T. Cost-effectiveness analysis of humanitarian relief in-terventions: visceral leishmaniasis treatment in the Sudan. Health Policy Plan. 1999; 14(1):70.
Desjeux P. Leishmaniasis: current situation and new perspectives. Comp Immunol Microbiol Infect Dis. 2004; 27(5):305-318.
Kar K. Serodiagnosis of leishmaniasis. Crit Rev Microbiol. 1995; 21(2):123-152.
Andre FE. Vaccinology: past achievements, pre-sent roadblocks and future promises. Vaccine. 2003; 21(7-8):593-595.
Mohebali, M. Javasian, E. Hashemi- Fesharki, R.Trial of non–living crude vaccine against zoo-notic cutaneous Leishmaniasis. Med J Islamic Rep Irn. 1995.8(4): 211-215.
Nadim, A., Javadian, E., Mohebali, M. The ex-perience of leishmanization in the Islamic Re-public of Iran. East Mediterr Health J 1997; 3(2).
Rafati S, Nakhaee A, Taheri T, Ghashghaii A, Salmanian AH, Jimenez M, Mohebali M, Ma-sina S, Fasel N. Expression of cysteine protei-nase type I and II of Leishmania infantum and their recognition by sera during canine and hu-man visceral Leishmaniasis. Exp Parasitol. 2003;103(3-4):143-51.
Mohebali M, Khamesipour A, Mobedi I, Zarei Z, Hashemi-Fesharki R. Double-blind rando-mized efficacy field trial of alum precipitated au-toclaved Leishmania major vaccine mixed with BCG against canine visceral Leishmaniasis in Meshkin-Shahr district, I.R. Iran. Vaccine. 2004; 22(29-30):4097-100.
Rezvan H, Rees R, Ali SA. Leishmania mexicana Gp63 cDNA Using Gene Gun Induced Higher Immunity to L. mexicana Infection Compared to Soluble Leishmania Antigen in BALB/C. Iranian J Parasitol. 2011; 6(4):60-75.
Cassataro J, Pasquevich KA, Estein SM et al. A recombinant subunit vaccine based on the inser-tion of 27 amino acids from Omp31 to the N-terminus of BLS induced a similar degree of protection against B. ovis than Rev.1 vaccina-tion. Vaccine. 2007; 25(22):4437.
Seay MB, Heard PL, Chaudhuri G. Surface Zn-proteinase as a molecule for defense of Leishma-nia mexicana amazonensis promastigotes against cy-tolysis inside macrophage phagolysosomes. In-fect Immun. 1996; 64(12):5129.
Ali SA, Rezvan H, McArdle SE, Khodadadi A, Asteal FA, Rees RC. CTL responses to Leishma-nia mexicana gp63-cDNA vaccine in a murine model. Parasite Immunol. 2009;31(7):373-83.
Rivier D, Bovay P, Shah R, Didisheim S, Mauël J. Vaccination against Leishmania major in a CBA mouse model of infection: role of adjuvants and mechanism of protection. Parasite Immunol. 1999; 21(9):461-73.
Inaba K, Inaba M, Romani N, Aya H, Deguchi M, Ikehara S, Muramatsu S, Steinman RM. Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor. J Exp Med. 1992; 176(6):1693-702.
Rojas JM, McArdle SE, Horton RB, Bell M, Mian S, Li G, Ali SA, Rees RC. Peptide immunisation of HLA-DR-transgenic mice permits the identification of a novel HLA-DRbeta1*0101- and HLA-DRbeta1*0401-restricted epitope from p53. Cancer Immunol Immunother. 2005; 54(3):243-253.
Spitzer N, Jardim A, Lippert D, Olafson RW. Long-term protection of mice against Leishmania major with a synthetic peptide vaccine. Vaccine. 1999; 17(11-12):1298-1300.
Rammensee H, Bachmann J, Emmerich NP, Bachor OA, Stevanovic S. SYFPEITHI: data-base for MHC ligands and peptide motifs. Im-munogenetics. 1999; 50(3-4):213-219.
Hundemer M, Schmidt S, Condomines M, Lupu A, Hose D, Moos M, Cremer F, Kleist C, Terness P, Belle S et al. Identification of a new HLA-A2-restricted T-cell epitope within HM1.24 as immunotherapy target for multiple myeloma. Exp Hematol. 2006; 34(4):486-496.
Mishra S, Sinha S. Prediction and molecular modeling of T-cell epitopes derived from pla-cental alkaline phosphatase for use in cancer immunotherapy. J Biomol Struct Dyn. 2006; 24(2):109-121.
Pelte C, Cherepnev G, Wang Y, Schoenemann C, Volk HD, Kern F. Random screening of proteins for HLA-A*0201-binding nine-amino acid peptides is not sufficient for identifying CD8 T cell epitopes recognized in the context of HLA-A*0201. J Immunol. 2004; 172(11): 6783-6789.
Ramage JM, Metheringham R, Moss R, Spen-dlove I, Rees R, Durrant LG. Comparison of the immune response to a self antigen after DNA immunisation of HLA*A201/H-2Kb and HHD transgenic mice. Vaccine. 2004; 22(13-14):1728-1731.
Van der Bruggen P, Bastin J, Gajewski T, Coulie PG, Boel P, De Smet C, Traversari C, Town-send A, Boon T. A peptide encoded by human gene MAGE-3 and presented by HLA-A2 in-duces cytolytic T lymphocytes that recognize tumor cells expressing MAGE-3. Eur J Im-munol. 1994; 24(12):3038-3043.
Firat H, Garcia-Pons F, Tourdot S, Pascolo S, Scardino A, Garcia Z, Michel ML, Jack RW, Jung G, Kosmatopoulos K et al. H-2 class I knockout, HLA-A2.1-transgenic mice: a versa-tile animal model for preclinical evaluation of an-titumor immunotherapeutic strategies. Eur J Immunol. 1999; 29(10):3112-3121.
Delespesse G, Yang LP, Ohshima Y, Demeure C, Shu U, Byun DG, Sarfati M. Maturation of human neonatal CD4+ and CD8+ T lympho-cytes into Th1/Th2 effectors. Vaccine. 1998; 16(14-15):1415-1419.
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Issue | Vol 8 No 2 (2013) | |
Section | Articles | |
Keywords | ||
FVB/N-DR1 transgenic mice NIFN-γ Leishmania major Peptide Proliferation gp63 |
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