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T-Cell Memory Responses Elicited by Yellow Fever Vaccine are Targeted to Overlapping Epitopes Containing Multiple HLA-I and -II Binding Motifs

de Melo, AB and Nascimento, EJM and Braga-Neto, U and Dhalia, R and Silva, AM and Oelke, M and Schneck, JP and Sidney, J and Sette, A and Montenegro, SML and Marques, ETA (2013) 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, 7 (1). ISSN 1935-2727

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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. © 2013 de Melo et al.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
de Melo, AB
Nascimento, EJMejmn@pitt.eduEJMN
Braga-Neto, U
Dhalia, R
Silva, AM
Oelke, M
Schneck, JP
Sidney, J
Sette, A
Montenegro, SML
Marques, ETAmarques@pitt.eduMARQUES0000-0003-3826-9358
Centers: Other Centers, Institutes, or Units > Center for Vaccine Research
Date: 1 January 2013
Date Type: Publication
Journal or Publication Title: PLoS Neglected Tropical Diseases
Volume: 7
Number: 1
DOI or Unique Handle: 10.1371/journal.pntd.0001938
Schools and Programs: Graduate School of Public Health > Infectious Diseases and Microbiology
Refereed: Yes
ISSN: 1935-2727
Other ID: NLM PMC3561163
PubMed Central ID: PMC3561163
PubMed ID: 23383350
Date Deposited: 14 Mar 2013 14:42
Last Modified: 24 Apr 2019 15:55
URI: http://d-scholarship.pitt.edu/id/eprint/17739

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