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Whole-Inactivated Influenza Virus Is a Potent Adjuvant for Influenza Peptides Containing CD8⁺ T Cell Epitopes.

ABSTRACT: Influenza peptide antigens coding for conserved T cell epitopes have the capacity to induce cross-protective influenza-specific immunity. Short peptide antigens used as a vaccine, however, often show poor immunogenicity. In this study, we demonstrate that whole-inactivated influenza virus (WIV) acts as an adjuvant for influenza peptide antigens, as shown by the induction of peptide-specific CD8⁺ T cells in HLA-A2.1 transgenic mice upon vaccination with the influenza-M1-derived GILGFVFTL peptide (GIL), formulated with WIV. By screening various concentrations of GIL and WIV, we found that both components contributed to the GIL-specific T cell response. Whereas co-localization of the peptide antigen and WIV adjuvant was found to be important, neither physical association between peptide and WIV nor fusogenic activity of WIV were relevant for the adjuvant effect of WIV. We furthermore show that WIV may adjuvate T cell responses to a variety of peptides, using pools of either conserved wild-type influenza peptides or chemically altered peptide ligands. This study shows the potential of WIV as an adjuvant for influenza peptides. The simple formulation process and the solid safety record of WIV make this an attractive adjuvant for T cell peptides, and may also be used for non-influenza antigens.

SUBMITTER: Soema PC

PROVIDER: S-EPMC5861146 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Whole-Inactivated Influenza Virus Is a Potent Adjuvant for Influenza Peptides Containing CD8<sup>+</sup> T Cell Epitopes.

Soema Peter C PC Rosendahl Huber Sietske K SK Willems Geert-Jan GJ Jacobi Ronald R Hendriks Marion M Soethout Ernst E Jiskoot Wim W de Jonge Jørgen J van Beek Josine J Kersten Gideon F A GFA Amorij Jean-Pierre JP

Frontiers in immunology 20180314

Influenza peptide antigens coding for conserved T cell epitopes have the capacity to induce cross-protective influenza-specific immunity. Short peptide antigens used as a vaccine, however, often show poor immunogenicity. In this study, we demonstrate that whole-inactivated influenza virus (WIV) acts as an adjuvant for influenza peptide antigens, as shown by the induction of peptide-specific CD8<sup>+</sup> T cells in HLA-A2.1 transgenic mice upon vaccination with the influenza-M1-derived GILGFVF ...[more]

PMID: 29593747

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Project description:Examining CD8+ and CD4+ T cell responses after primary Yellow Fever vaccination in a cohort of 210 volunteers, we have identified and tetramer-validated 92 CD8+ and 50 CD4+ T cell epitopes, many inducing strong and prevalent (i.e., immunodominant) T cell responses. Restricted by 40 and 14 HLA-class I and II allotypes, respectively, these responses have wide population coverage and might be of considerable academic, diagnostic and therapeutic interest. The broad coverage of epitopes and HLA overcame the otherwise confounding effects of HLA diversity and non-HLA background providing the first evidence of T cell immunodomination in humans. Also, double-staining of CD4+ T cells with tetramers representing the same HLA-binding core, albeit with different flanking regions, demonstrated an extensive diversification of the specificities of many CD4+ T cell responses. We suggest that this could reduce the risk of pathogen escape, and that multi-tetramer staining is required to reveal the true magnitude and diversity of CD4+ T cell responses. Our T cell epitope discovery approach uses a combination of (1) overlapping peptides representing the entire Yellow Fever virus proteome to search for peptides containing CD4+ and/or CD8+ T cell epitopes, (2) predictors of peptide-HLA binding to suggest epitopes and their restricting HLA allotypes, (3) generation of peptide-HLA tetramers to identify T cell epitopes, and (4) analysis of ex vivo T cell responses to validate the same. This approach is systematic, exhaustive, and can be done in any individual of any HLA haplotype. It is all-inclusive in the sense that it includes all protein antigens and peptide epitopes, and encompasses both CD4+ and CD8+ T cell epitopes. It is efficient and, importantly, reduces the false discovery rate. The unbiased nature of the T cell epitope discovery approach presented here should support the refinement of future peptide-HLA class I and II predictors and tetramer technologies, which eventually should cover all HLA class I and II isotypes. We believe that future investigations of emerging pathogens (e.g., SARS-CoV-2) should include population-wide T cell epitope discovery using blood samples from patients, convalescents and/or long-term survivors, who might all hold important information on T cell epitopes and responses.

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Whole-Inactivated Influenza Virus Is a Potent Adjuvant for Influenza Peptides Containing CD8⁺ T Cell Epitopes.

Publications

Whole-Inactivated Influenza Virus Is a Potent Adjuvant for Influenza Peptides Containing CD8<sup>+</sup> T Cell Epitopes.

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Whole-Inactivated Influenza Virus Is a Potent Adjuvant for Influenza Peptides Containing CD8+ T Cell Epitopes.

Publications

Whole-Inactivated Influenza Virus Is a Potent Adjuvant for Influenza Peptides Containing CD8<sup>+</sup> T Cell Epitopes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

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Whole-Inactivated Influenza Virus Is a Potent Adjuvant for Influenza Peptides Containing CD8⁺ T Cell Epitopes.