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PROMISCUOUS T-CELL EPITOPES OF PLASMODIUM MEROZOITE SURFACE PROTEIN 9 (PVMSP9) INDUCES IFN-γ AND IL-4 RESPONSES IN INDIVIDUALS NATURALLY EXPOSED TO MALARIA IN THE BRAZILIAN AMAZON
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Affilliation
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunoparasitologia. Rio de Janeiro, RJ. Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa em Malária. Rio de Janeiro, RJ. Brasil.
Emory University. Emory Vaccine Center. Atlanta, GA, USA.
Emory University. Emory Vaccine Center. Atlanta, GA, USA.
Universidade Federal Fluminense. Instituto de Biologia. Departamento de Biologia Celular e Molecular. Niterói, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Proteínas e Peptídeos. Rio de Janeiro, RJ, Brasil.
LACEN. Departamento de Entomologia. Porto Velho, RO, Brasil.
Universidade do Estado do Rio de Janeiro. Laboratório de Histocompatibilidade e Criopreservação. Rio de Janeiro, RJ, Brasil.
Universidade do Estado do Rio de Janeiro. Laboratório de Histocompatibilidade e Criopreservação. Rio de Janeiro, RJ, Brasil.
Emory University. Emory Vaccine Center. Atlanta, GA, USA / Emory University Shool of Medicine. Division of Infectious Diseases. Atlanta, GA, USA.
CDC/National Center for Infectious Diseases.
Emory University. Emory Vaccine Center. Atlanta, GA, USA / Emory University Shool of Medicine. Division of Infectious Diseases. Atlanta, GA, USA.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunoparasitologia. Rio de Janeiro, RJ. Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa em Malária. Rio de Janeiro, RJ. Brasil.
Emory University. Emory Vaccine Center. Atlanta, GA, USA.
Emory University. Emory Vaccine Center. Atlanta, GA, USA.
Universidade Federal Fluminense. Instituto de Biologia. Departamento de Biologia Celular e Molecular. Niterói, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Proteínas e Peptídeos. Rio de Janeiro, RJ, Brasil.
LACEN. Departamento de Entomologia. Porto Velho, RO, Brasil.
Universidade do Estado do Rio de Janeiro. Laboratório de Histocompatibilidade e Criopreservação. Rio de Janeiro, RJ, Brasil.
Universidade do Estado do Rio de Janeiro. Laboratório de Histocompatibilidade e Criopreservação. Rio de Janeiro, RJ, Brasil.
Emory University. Emory Vaccine Center. Atlanta, GA, USA / Emory University Shool of Medicine. Division of Infectious Diseases. Atlanta, GA, USA.
CDC/National Center for Infectious Diseases.
Emory University. Emory Vaccine Center. Atlanta, GA, USA / Emory University Shool of Medicine. Division of Infectious Diseases. Atlanta, GA, USA.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunoparasitologia. Rio de Janeiro, RJ. Brasil.
Abstract
Plasmodium vivax merozoite surface protein (PvMSP9) stimulates both cellular and humoral
immune responses in individuals who are naturally infected by this parasite species. To identify
immunodominant human T-cell epitopes in PvMSP9, we used the MHC class II binding peptide
prediction algorithm ProPred. Eleven synthetic peptides representing predicted putative
promiscuous T cell epitopes were tested in IFN-γ and IL-4 ELISPOT assays using peripheral
blood mononuclear cells (PBMC) derived from 142 individuals from Rondonia State, Brazil who
had been naturally exposed to P. vivax infections. To determine whether the predicted epitopes are
preferentially recognized in the context of multiple alleles, MHC Class II typing of the cohort was
also performed. Five synthetic peptides elicited robust cellular responses, and the overall
frequencies of IFN-γ and IL-4 responders to at least one of the promiscuous peptides were 62%
and 46%, respectively. The frequencies of IFN-γ and IL-4 responders to each peptide were not
associated with a particular HLA-DRB1 allelic group since most of the peptides induced a
response in individuals of 12 out of 13 studied allelic groups. The prediction of promiscuous
epitopes using ProPred led to the identification of immunodominant epitopes recognized by
PBMC from a significant proportion of a genetically heterogeneous population exposed to malaria infections. The combination of several such T-cell epitopes in a vaccine construct may increase
the frequency of responders and the overall efficacy of subunit vaccines in genetically distinct
populations.
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