Identification of immunodominant T cell epitopes induced by natural Zika virus infection.
| Title: | Identification of immunodominant T cell epitopes induced by natural Zika virus infection. |
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| Authors: | Eickhoff CS; Department of Internal Medicine, Saint Louis University, Division of Infectious Diseases, Allergy, and Immunology, Saint Louis, MO, United States.; Meza KA; Department of Internal Medicine, Saint Louis University, Division of Infectious Diseases, Allergy, and Immunology, Saint Louis, MO, United States.; Terry FE; EpiVax, Inc., Providence, RI, United States.; Colbert CG; Department of Internal Medicine, Saint Louis University, Division of Infectious Diseases, Allergy, and Immunology, Saint Louis, MO, United States.; Blazevic A; Department of Internal Medicine, Saint Louis University, Division of Infectious Diseases, Allergy, and Immunology, Saint Louis, MO, United States.; Gutiérrez AH; EpiVax, Inc., Providence, RI, United States.; Stone ET; Department of Molecular Microbiology and Immunology, Saint Louis University, Saint Louis, MO, United States.; Brien JD; Department of Molecular Microbiology and Immunology, Saint Louis University, Saint Louis, MO, United States.; Pinto AK; Department of Molecular Microbiology and Immunology, Saint Louis University, Saint Louis, MO, United States.; El Sahly HM; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, United States.; Mulligan MJ; New York University Grossman School of Medicine, Division of Infectious Diseases and Immunology, New York, NY, United States.; Rouphael N; Emory University School of Medicine, Division of Infectious Diseases, Department of Internal Medicine, Atlanta, GA, United States.; Alcaide ML; University of Miami, Division of Infectious Diseases, Miller School of Medicine, Miami, FL, United States.; Tomashek KM; Division of Microbiology, Immunology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD, United States.; Focht C; The Emmes Company, LLC., Rockville, MD, United States.; Martin WD; EpiVax, Inc., Providence, RI, United States.; Moise L; EpiVax, Inc., Providence, RI, United States.; De Groot AS; EpiVax, Inc., Providence, RI, United States.; University of Georgia Center for Vaccines and Immunology, Athens, GA, United States.; Hoft DF; Department of Internal Medicine, Saint Louis University, Division of Infectious Diseases, Allergy, and Immunology, Saint Louis, MO, United States.; Department of Molecular Microbiology and Immunology, Saint Louis University, Saint Louis, MO, United States. |
| Source: | Frontiers in immunology [Front Immunol] 2023 Aug 29; Vol. 14, pp. 1247876. Date of Electronic Publication: 2023 Aug 29 (Print Publication: 2023). |
| Publication Type: | Journal Article; Research Support, N.I.H., Extramural |
| Language: | English |
| Journal Info: | Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [Lausanne : Frontiers Research Foundation] |
| MeSH Terms: | Zika Virus Infection* ; Zika Virus* ; Aedes*; Adult ; Animals ; Female ; Pregnancy ; Humans ; Epitopes, T-Lymphocyte ; Genes, MHC Class I |
| 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.; (Copyright © 2023 Eickhoff, Meza, Terry, Colbert, Blazevic, Gutiérrez, Stone, Brien, Pinto, El Sahly, Mulligan, Rouphael, Alcaide, Tomashek, Focht, Martin, Moise, De Groot and Hoft.) |
| Competing Interests: | MM reported laboratory research and clinical trials contract funding with Lilly, Pfizer, and Sanofi; and personal fees for Scientific Advisory Board service from Merck, Meissa Vaccines, Inc. and Pfizer. Authors FT, AG, WM, LM, and ADG are (or were) employed by EpiVax, Inc, and author CF was employed by The Emmes Company, LLC. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. |
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| Grant Information: | HHSN272201300021I United States AI NIAID NIH HHS; HHSN272201300018I United States AI NIAID NIH HHS; HHSN272201300015I United States AI NIAID NIH HHS; P30 AI073961 United States AI NIAID NIH HHS |
| Contributed Indexing: | Keywords: EpiMatrix; JanusMatrix; T cell; Zika virus; epitopes; immunodominance; immunoinformatics |
| Substance Nomenclature: | 0 (Epitopes, T-Lymphocyte) |
| Entry Date(s): | Date Created: 20230914 Date Completed: 20230915 Latest Revision: 20230916 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC10497216 |
| DOI: | 10.3389/fimmu.2023.1247876 |
| PMID: | 37705976 |
| Database: | MEDLINE |
Journal Article; Research Support, N.I.H., Extramural