Open AccessDesign of multi-epitope peptides containing HLA class-I and class-II-restricted epitopes derived from immunogenic Leishmania proteins, and evaluation of CD4+ and CD8+ T cell responses induced in cured cutaneous leishmaniasis subjects
Author(s) -
Sarra Hamrouni,
Rachel Bras-Gonçalves,
Abdelhamid Kidar,
Abdul Karim,
Rym Chamakh-Ayari,
Elodie Petitdidier,
Yasmine Messaoudi,
Julie Pagniez,
Jean-Loup Lemesre,
Amel Meddeb-Garnaoui
Publication year - 2020
Publication title -
plos neglected tropical diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.99
H-Index - 135
eISSN - 1935-2735
pISSN - 1935-2727
DOI - 10.1371/journal.pntd.0008093
Subject(s) - epitope , elispot , biology , cd8 , human leukocyte antigen , immunology , antigen , t cell , leishmania major , immune system , cutaneous leishmaniasis , cytotoxic t cell , virology , leishmania , leishmaniasis , biochemistry , parasite hosting , world wide web , computer science , in vitro
Human leishmaniasis is a public health problem worldwide for which the development of a vaccine remains a challenge. T cell-mediated immune responses are crucial for protection. Peptide vaccines based on the identification of immunodominant T cell epitopes able to induce T cell specific immune responses constitute a promising strategy. Here, we report the identification of human leukocyte antigen class-I (HLA-I) and -II (HLA-II)-restricted multi-epitope peptides from Leishmania proteins that we have previously described as vaccine candidates. Promastigote Surface Antigen (PSA), LmlRAB ( L . major large RAB GTPase) and Histone (H2B) were screened, in silico , for T cell epitopes. 6 HLA-I and 5 HLA-II-restricted multi-epitope peptides, able to bind to the most frequent HLA molecules, were designed and used as pools to stimulate PBMCs from individuals with healed cutaneous leishmaniasis. IFN-γ, IL-10, TNF-α and granzyme B (GrB) production was evaluated by ELISA/CBA. The frequency of IFN-γ-producing T cells was quantified by ELISpot. T cells secreting cytokines and memory T cells were analyzed by flow cytometry. 16 of 25 peptide pools containing HLA-I, HLA-II or HLA-I and -II peptides were able to induce specific and significant IFN-γ levels. No IL-10 was detected. 6 peptide pools were selected among those inducing the highest IFN-γ levels for further characterization. 3/6 pools were able to induce a significant increase of the percentages of CD4+IFN-γ+, CD8+IFN-γ+ and CD4+GrB+ T cells. The same pools also induced a significant increase of the percentages of bifunctional IFN-γ+/TNF-α+CD4+ and/or central memory T cells. We identified highly promiscuous HLA-I and -II restricted epitope combinations from H2B, PSA and LmlRAB proteins that stimulate both CD4+ and CD8+ T cell responses in recovered individuals. These multi-epitope peptides could be used as potential components of a polytope vaccine for human leishmaniasis.