2.1 Development of a multi-epitope peptide vaccine against human leishmaniasis

Institut de recherche pour le développement (IRD), Montpellier, France   - Institut Pasteur de Tunis (IPT), Tunisia, Tunis   - Synprosis cGMP, Fuveau, France

Area of research: Prevention
Research programme: Basic Science

Objectives:

(1) To characterize human immune responses in three groups exposed to Leishmania infantum or L. major in Tunisia: a) drug-cured patients (recovered); b) asymptomatic persons with positive Leishmania-specific lymphoprolipherative test (TTL+); and c) TTL-negative household contacts. (2) To evaluate cytokine responses to novel immunodominant HLA-I or HLA-II restricted peptides derived from three promising antigens, with information on immunological correlates of protection, by using peripheral mononuclear cells from individuals who have developed immunity to Leishmania

Expected results:

(1) To provide important clues to the type of immunity that a successful vaccine will need to elicit 

(2) To select potential peptides with multiple and appropriate immunodominant epitopes to be used (together or some of them) as antigens for clinical development of a multi-epitope peptide vaccine against human leishmaniases.

Summary:

Background: No vaccine exists against any form of human leishmaniasis. Recovery from infection is usually accompanied by a strong life-long immunity, indicating that a vaccine is feasible. In addition, many exposed infected people remain asymptomatic and develop a specific cell-mediated immune response17. We hypothesized that people resistant to Leishmania infection (immune asymptomatic and cured individuals) might hold the key to evaluate a vaccine from human cells involved in protective immune responses. 

Methodology: TMulti-HLA-restricted polyepitopic peptides targeting severe forms of human leishmaniasis and ensuring the best concerned world population coverage will be designed by in silico analysis, in vitro peptide binding to HLA molecules and ex vivo immunogenicity. Total soluble leishmania antigen or different peptides combinations will be evaluated for their ability to elicit an ex vivo cellular immune response in PBMC or blood from previously exposed individuals with evidence of protective immunity in comparison with non-exposed subjects.