Evaluation of T cell responses to naturally processed variant SARS-CoV-2 spike antigens in individuals following infection or vaccination.
Yin Z., Chen J-L., Lu Y., Wang B., Godfrey L., Mentzer AJ., Yao X., Liu G., Wellington D., Zhao Y., Wing PAC., Dejnirattisa W., Supasa P., Liu C., Hublitz P., Beveridge R., Waugh C., Clark S-A., Clark K., Sopp P., Rostron T., Mongkolsapaya J., Screaton GR., Ogg G., Ewer K., Pollard AJ., Gilbert S., Knight JC., Lambe T., Smith GL., Dong T., Peng Y.
Most existing studies characterizing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cell responses are peptide based. This does not allow evaluation of whether tested peptides are processed and presented canonically. In this study, we use recombinant vaccinia virus (rVACV)-mediated expression of SARS-CoV-2 spike protein and SARS-CoV-2 infection of angiotensin-converting enzyme (ACE)-2-transduced B cell lines to evaluate overall T cell responses in a small cohort of recovered COVID-19 patients and uninfected donors vaccinated with ChAdOx1 nCoV-19. We show that rVACV expression of SARS-CoV-2 antigen can be used as an alternative to SARS-CoV-2 infection to evaluate T cell responses to naturally processed spike antigens. In addition, the rVACV system can be used to evaluate the cross-reactivity of memory T cells to variants of concern (VOCs) and to identify epitope escape mutants. Finally, our data show that both natural infection and vaccination could induce multi-functional T cell responses with overall T cell responses remaining despite the identification of escape mutations.