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Abstract

Assessment of Protection Induced by DNA and Live Vaccine Encoding Leishmania MHC Class I Restricted Epitopes against L. major Challenge in Balb/c Mice Model

Mojgan Zandieh, Tahereh Kashi, Tahereh Taheri, Farnaz Zahedifard, Yasaman Taslimi, Mahnaz Doustdary, Sima Habibzadeh, Ali Eslamifar, Fazel Shokri, Sima Rafati and Negar Seyed

Leishmaniasis is a neglected tropical disease endemic in more than 88 countries and is spreading over and over mainly due to transmigration and drug resistance. Unfortunately, despite increasing incidence, effective vaccine is still lagging behind. Unraveling CD8+ T-cells’ contribution in infection control has recently led a new concept into Leishmania vaccine research field as T-cell vaccine. Therefore we studied the efficacy of a CD8 stimulating T-cell vaccine (a string of beads) in two distinctive approaches as homologous DNA-DNA or heterologous DNALive prime-boost strategies. Here we hypothesized that CD8+ T-cell stimulation by polytope constructs diverts primary Th2 responses into Th1 resulting in disease control. Four recently reported H-2Kd restricted epitopes from proteins out of Leishmania vaccine candidate repertoire were included in the polytope construct (besides 13 HLA-A2 restricted peptides from Leishmania well known vaccine candidates). Protective effect of the polytope construct was evaluated by clinical (footpad swelling and parasite burden) and immunological (IFN-γ/IL-5 ELISA, IFN-γ ICCS and CFSE) assays after L. majorEGFP infectious challenge of Balb/c mice. In this study, DNA-DNA prime-boost regimen specifically stimulated CD8+ T-cells resulting in partial protection in test group compared to controls. Protective effect was clearly compromised by CD8+ T-cell depletion at the time of infectious challenge resulting in predominant Th2 response. This directly confirmed CD8+ T-cells’ role in early stage Th1 response polarization. Heterologous primeboost regimen (DNA priming and live L. tarPT-EGFP boosting), however was less effective inducing CD8+ T-cells and partial protection induced did not last long. These preliminary results for polytope constructs seem as sparkles of hope in Leishmania vaccination.