Publication

Identification of immunodominant T cell epitopes induced by natural Zika virus infection

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Last modified
  • 06/25/2025
Type of Material
Authors
    Christopher S. Eickhoff, Saint Louis UniversityKrystal A. Meza, Saint Louis UniversityFrances E. Terry, EpiVax IncorporatedChase G. Colbert, Saint Louis UniversityAzra Blazevic, Saint Louis UniversityAndres H. Gutiérrez, EpiVax IncorporatedE. Taylor Stone, Saint Louis UniversityJames D. Brien, Saint Louis UniversityAmelia K. Pinto, Saint Louis UniversityHana M. El Sahly, Baylor College of MedicineMark Mulligan, Emory UniversityNadine Rouphael, Emory UniversityMaria L. Alcaide, University of MiamiKay M. Tomashek, National Institute of Allergy and Infectious Diseases (NIAID)Chris Focht, The Emmes Company, LLCWilliam D. Martin, EpiVax IncorporatedLeonard Moise, EpiVax IncorporatedAnne S. De Groot, EpiVax IncorporatedDaniel F. Hoft, Saint Louis University
Language
  • English
Date
  • 2023-01-01
Publisher
  • Frontiers
Publication Version
Copyright Statement
  • © 2023 Eickhoff, Meza, Terry, Colbert, Blazevic, Gutiérrez, Stone, Brien, Pinto, El Sahly, Mulligan, Rouphael, Alcaide, Tomashek, Focht, Martin, Moise, De Groot and Hoft
License
Final Published Version (URL)
Title of Journal or Parent Work
Volume
  • 14
Start Page
  • 1247876
End Page
  • 1247876
Grant/Funding Information
  • This work was supported by NIH funds HHSN272201300021I and HHSN27200013 to DH, HHSN27200012 to MA, HHSN272201300018I and HHSN27200011 to NR, and HHSN272201300015I and HHSN27200008 to HS; and Miami CFAR P30AI073961 to MA.
Supplemental Material (URL)
Abstract
  • Zika virus (ZIKV) is a flavivirus primarily transmitted by Aedes species mosquitoes, first discovered in Africa in 1947, that disseminated through Southeast Asia and the Pacific Islands in the 2000s. The first ZIKV infections in the Americas were identified in 2014, and infections exploded through populations in Brazil and other countries in 2015/16. ZIKV infection during pregnancy can cause severe brain and eye defects in offspring, and infection in adults has been associated with higher risks of Guillain-Barré syndrome. We initiated a study to describe the natural history of Zika (the disease) and the immune response to infection, for which some results have been reported. In this paper, we identify ZIKV-specific CD4+ and CD8+ T cell epitopes that induce responses during infection. Two screening approaches were utilized: an untargeted approach with overlapping peptide arrays spanning the entire viral genome, and a targeted approach utilizing peptides predicted to bind human MHC molecules. Immunoinformatic tools were used to identify conserved MHC class I supertype binders and promiscuous class II binding peptide clusters predicted to bind 9 common class II alleles. T cell responses were evaluated in overnight IFN-γ ELISPOT assays. We found that MHC supertype binding predictions outperformed the bulk overlapping peptide approach. Diverse CD4+ T cell responses were observed in most ZIKV-infected participants, while responses to CD8+ T cell epitopes were more limited. Most individuals developed a robust T cell response against epitopes restricted to a single MHC class I supertype and only a single or few CD8+ T cell epitopes overall, suggesting a strong immunodominance phenomenon. Noteworthy is that many epitopes were commonly immunodominant across persons expressing the same class I supertype. Nearly all of the identified epitopes are unique to ZIKV and are not present in Dengue viruses. Collectively, we identified 31 immunogenic peptides restricted by the 6 major class I supertypes and 27 promiscuous class II epitopes. These sequences are highly relevant for design of T cell-targeted ZIKV vaccines and monitoring T cell responses to Zika virus infection and vaccination.
Author Notes
Keywords
Research Categories
  • Biology, Virology
  • Health Sciences, Obstetrics and Gynecology
  • Biology, Cell
  • Biology, Genetics

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