Highly conserved, non-human-like, and cross-reactive SARS-CoV-2 T cell epitopes for COVID-19 vaccine design and validation

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 associ...

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Bibliographic Details
Published in:npj vaccines 2021-05, Vol.6 (1), p.71-71, Article 71
Main Authors: Meyers, Lauren M., Gutiérrez, Andres H., Boyle, Christine M., Terry, Frances, McGonnigal, Bethany G., Salazar, Andres, Princiotta, Michael F., Martin, Wiliam D., De Groot, Anne S., Moise, Leonard
Format: Article
Language:English
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631/250/590/2030
692/699/255/2514
Biomedical and Life Sciences
Biomedicine
COVID-19
COVID-19 vaccines
Immune system
Immunization
Infectious Diseases
Medical Microbiology
Peptides
Public Health
Respiratory diseases
Severe acute respiratory syndrome coronavirus 2
Vaccine
Vaccines
Virology
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Summary: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.
ISSN:2059-0105
2059-0105
DOI:10.1038/s41541-021-00331-6