A glimpse into the diverse cellular immunity against SARS-CoV-2 

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific cellular immune response may prove to be essential for long-term immune protection against the novel coronavirus disease 2019 (COVID-19). To assess COVID-19-specific immunity in the population, we synthesized selected peptide pools of SARS-CoV-2 structural and functional proteins, including Spike (S), Membrane (M), envelope (E), Nucleocapsid (N) and Protease (P) as target antigens. Survey of the T cell precursur frequencies in healthy individuals specific to these viral antigens demonstrated a diverse cellular immunity, including high, medium, low and no responders. This was further confirmed by in vitro induction of anti-SARS-CoV-2 T cell immune responses using dendritic cell (DC)/T cell coculture, which was consistent with the corresponding T cell precursor frequencies in each individual tested. In general, the combination of all five antigenic pools induced the strongest cellular immune response, and individual donors responded differently to different viral antigens. Importantly, a secondary in vitro booster stimulation of the T cells with the DC-peptides induced increased anti-viral immune responses in all individuals even in the no responders, suggesting that booster immunization in a vaccine scheme may elicit a broad protection in immune naïve population. Our analysis illustrates the critical role of cellular immunity in fighting COVID-19 and the importance of analyzing anti-SARS-CoV-2 T cell response in addition to antibody response in the population.