Natural and vaccine-induced SARS-CoV-2 immunity in humans has been described but correlates of protection are not yet defined. T cells support the SARS-CoV-2 antibody response, clear virus-infected cells, and may be required to block transmission. In this study, we identified peptide epitopes associated with SARS-CoV-2 T-cell immunity. Using immunoinformatic methods, T-cell epitopes from spike, membrane, and envelope were selected for maximal HLA-binding potential, coverage of HLA diversity, coverage of circulating virus, and minimal potential cross-reactivity with self. Direct restimulation of PBMCs collected from SARS-CoV-2 convalescents confirmed 66% of predicted epitopes, whereas only 9% were confirmed in naive individuals. However, following a brief period of epitope-specific T-cell expansion, both cohorts demonstrated robust T-cell responses to 97% of epitopes. HLA-DR3 transgenic mouse immunization with peptides co-formulated with poly-ICLC generated a potent Th1-skewed, epitope-specific memory response, alleviating safety concerns of enhanced respiratory disease associated with Th2 induction. Taken together, these epitopes may be used to improve our understanding of natural and vaccine-induced immunity, and to facilitate the development of T-cell-targeted vaccines that harness pre-existing SARS-CoV-2 immunity.
【저자키워드】 viral infection, Peptide vaccines, 【초록키워드】 SARS-CoV-2, Vaccine, Antibody Response, T-cell Response, Human, Th2, peptide, Transmission, virus, immunization, SARS-CoV-2 immunity, cross-reactivity, Epitopes, Cohort, T cell, Coverage, Respiratory disease, membrane, PBMC, HLA, T-cell, convalescent, epitope, T-cell epitope, T-cell immunity, memory response, Vaccine-induced immunity, Support, natural, virus-infected cells, circulating, Direct, Transgenic mouse, robust, IMPROVE, selected, defined, described, predicted, collected, required, facilitate, demonstrated, individuals, HLA-DR3, peptide epitope, the SARS-CoV-2, 【제목키워드】 SARS-CoV-2, T cell epitope, cross-reactive, COVID-19 vaccine design, conserved,