Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/23667
Title: T-cell memory responses elicited by yellow fever vaccine are targeted to overlapping epitopes containing multiple HLA-I and -II binding motifs
Authors: Melo, Andréa Barbosa de
Nascimento, Eduardo J. M.
Braga-Neto, Ulisses
Dhalia, Rafael
Silva, Ana Maria
Oelke, Mathias
Schneck, Jonathan P.
Sidney, John
Sette, Alessandro
Montenegro, Silvia M. L.
Marques, Ernesto T. A.
Affilliation: Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Laboratório de Virologia e Terapia Experimental. Recife, PE, Brasil.
University of Pittsburgh. Center for Vaccine Research. Department of Infectious Diseases and Microbiology. Pittsburgh, Pennsylvania, United States of America.
Texas A&M University. College Station. Department of Electrical and Computer Engineering. Texas, United States of America.
Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Laboratório de Virologia e Terapia Experimental. Recife, PE, Brasil.
Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Laboratório de Virologia e Terapia Experimental. Recife, PE, Brasil.
The Johns Hopkins University School of Medicine. Department of Pathology. Baltimore, Maryland, United States of America.
The Johns Hopkins University School of Medicine. Department of Pathology. Baltimore, Maryland, United States of America.
La Jolla Institute for Allergy and Immunology. Vaccine Discovery. La Jolla, California, United States of America.
La Jolla Institute for Allergy and Immunology. Vaccine Discovery. La Jolla, California, United States of America.
Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Departamento de imunologia. Recife, PE, Brasil.
Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Laboratório de Virologia e Terapia Experimental. Recife, PE, Brasil / University of Pittsburgh. Center for Vaccine Research. Department of Infectious Diseases and Microbiology. Pittsburgh, Pennsylvania, United States of America.
Abstract: The yellow fever vaccines (YF-17D-204 and 17DD) are considered to be among the safest vaccines and the presence of neutralizing antibodies is correlated with protection, although other immune effector mechanisms are known to be involved. T-cell responses are known to play an important role modulating antibody production and the killing of infected cells. However, little is known about the repertoire of T-cell responses elicited by the YF-17DD vaccine in humans. In this report, a library of 653 partially overlapping 15-mer peptides covering the envelope (Env) and nonstructural (NS) proteins 1 to 5 of the vaccine was utilized to perform a comprehensive analysis of the virus-specific CD4(+) and CD8(+) T-cell responses. The T-cell responses were screened ex-vivo by IFN-γ ELISPOT assays using blood samples from 220 YF-17DD vaccinees collected two months to four years after immunization. Each peptide was tested in 75 to 208 separate individuals of the cohort. The screening identified sixteen immunodominant antigens that elicited activation of circulating memory T-cells in 10% to 33% of the individuals. Biochemical in-vitro binding assays and immunogenetic and immunogenicity studies indicated that each of the sixteen immunogenic 15-mer peptides contained two or more partially overlapping epitopes that could bind with high affinity to molecules of different HLAs. The prevalence of the immunogenicity of a peptide in the cohort was correlated with the diversity of HLA-II alleles that they could bind. These findings suggest that overlapping of HLA binding motifs within a peptide enhances its T-cell immunogenicity and the prevalence of the response in the population. In summary, the results suggests that in addition to factors of the innate immunity, "promiscuous" T-cell antigens might contribute to the high efficacy of the yellow fever vaccines.
Keywords: yellow fever
cytology
Vaccine
CD4
keywords: Febre Amarela
citologia
Vacinas
CD4
DeCS: Epitopos de Linfócito T
imunologia
Antígenos de Histocompatibilidade Classe II
imunologia
Antígenos de Histocompatibilidade Classe I
imunologia
Memória Imunológica
Humanos
Linfócitos T
imunologia
Vacina contra Febre Amarela
imunologia
Interferon gama
secreção
Vacina contra Febre Amarela
administração & dosagem
ELISPOT
Issue Date: 2013
Publisher: Alan L. Rothman
Citation: MELO, A. B. de et al. T-cell memory responses elicited by yellow fever vaccine are targeted to overlapping epitopes containing multiple HLA-I and -II binding motifs. PLoS neglected tropical diseases, v. 7, n. 1, p. e1938, 2013.
DOI: 10.1371/journal.pntd.0001938
ISSN: 1935-2735
Copyright: open access
Appears in Collections:PE - IAM - Artigos de Periódicos
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