@article{fdi:010079053,
  title = {{D}esign of multi-epitope peptides containing {HLA} class-{I} and class-{II}-restricted epitopes derived from immunogenic {L}eishmania proteins, and evaluation of {CD}4+and {CD}8+{T} cell responses induced in cured cutaneous leishmaniasis subjects},
  author = {{H}amrouni, {S}. and {B}ras {G}oncalves, {R}achel and {K}idar, {A}. and {A}oun, {K}. and {C}hamakh-{A}yari, {R}. and {P}etitdidier, {E}lodie and {M}essaoudi, {Y}. and {P}agniez, {J}ulie and {L}emesre, {J}ean-{L}oup and {M}eddeb-{G}arnaoui, {A}.},
  editor = {},
  language = {{ENG}},
  abstract = {{A}uthor summary {T}he control of leishmaniasis, a neglected tropical disease of public health importance, caused by protozoan parasites of the genus {L}eishmania, mainly relies on chemotherapy, which is highly toxic. {C}urrently, there is no vaccine against human leishmaniasis. {P}eptide-based vaccines consisting of {T} cell epitopes identified within proteins of interest by epitope predictive algorithms are a promising strategy for vaccine development. {H}ere, we identified multi-epitope peptides composed of {HLA}-{I} and -{II}-restricted epitopes, using immunoinformatic tools, within {L}eishmania proteins previously described as potential vaccine candidates. {W}e showed that multi-epitope peptides used as pools were able to activate {IFN}-gamma producing {CD}4+ as well as {CD}8+ {T} cells, both required for parasite elimination. {I}n addition, granzyme {B}-producing {CD}4+ {T} cells, bifunctional {CD}4+ {IFN}-gamma+/{TNF}-alpha+ and/or {TNF}-alpha+/{IL}-2+ {T} cells as well as {CD}4+ and {CD}8+ central memory {T} cells, all involved in {L}eishmania infection control, were significantly increased in response to multi-epitope peptide stimulation. {A}s far as we know, no study has described the detection of both {CD}4+ and {CD}8+ {T} cell populations in response to stimulation by both {HLA}-{I} and {II}-restricted peptides in humans. {T}he immunogenic {HLA}-{I} and -{II}-restricted multi-epitope peptides identified in this study could constitute potential vaccine candidates against human leishmaniasis. {H}uman 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. {P}eptide vaccines based on the identification of immunodominant {T} cell epitopes able to induce {T} cell specific immune responses constitute a promising strategy. {H}ere, we report the identification of human leukocyte antigen class-{I} ({HLA}-{I}) and -{II} ({HLA}-{II})-restricted multi-epitope peptides from {L}eishmania proteins that we have previously described as vaccine candidates. {P}romastigote {S}urface {A}ntigen ({PSA}), {L}ml{RAB} ({L}. major large {RAB} {GTP}ase) and {H}istone ({H}2{B}) 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 {PBMC}s from individuals with healed cutaneous leishmaniasis. {IFN}-gamma, {IL}-10, {TNF}-alpha and granzyme {B} ({G}r{B}) production was evaluated by {ELISA}/{CBA}. {T}he frequency of {IFN}-gamma-producing {T} cells was quantified by {ELIS}pot. {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}-gamma levels. {N}o {IL}-10 was detected. 6 peptide pools were selected among those inducing the highest {IFN}-gamma levels for further characterization. 3/6 pools were able to induce a significant increase of the percentages of {CD}4+{IFN}-gamma+, {CD}8+{IFN}-gamma+ and {CD}4+{G}r{B}+ {T} cells. {T}he same pools also induced a significant increase of the percentages of bifunctional {IFN}-gamma+/{TNF}-alpha+{CD}4+ and/or central memory {T} cells. {W}e identified highly promiscuous {HLA}-{I} and -{II} restricted epitope combinations from {H}2{B}, {PSA} and {L}ml{RAB} proteins that stimulate both {CD}4+ and {CD}8+ {T} cell responses in recovered individuals. {T}hese multi-epitope peptides could be used as potential components of a polytope vaccine for human leishmaniasis.},
  keywords = {},
  booktitle = {},
  journal = {{PL}o{S} {N}eglected {T}ropical {D}iseases},
  volume = {14},
  numero = {3},
  pages = {e0008093 [31 ]},
  ISSN = {1935-2735},
  year = {2020},
  DOI = {10.1371/journal.pntd.0008093},
  URL = {https://www.documentation.ird.fr/hor/fdi:010079053},
}