Impact of SARS-CoV-2 variants on the total CD4+ and CD8+ T cell reactivity in infected or vaccinated individuals

• Published in: Cell reports. Medicine 2021-07, Vol.2 (7), p.100355-100355, Article 100355
• Main Authors: Tarke, Alison, Sidney, John, Methot, Nils, Yu, Esther Dawen, Zhang, Yun, Dan, Jennifer M., Goodwin, Benjamin, Rubiro, Paul, Sutherland, Aaron, Wang, Eric, Frazier, April, Ramirez, Sydney I., Rawlings, Stephen A., Smith, Davey M., da Silva Antunes, Ricardo, Peters, Bjoern, Scheuermann, Richard H., Weiskopf, Daniela, Crotty, Shane, Grifoni, Alba, Sette, Alessandro
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; CD4; CD4-Positive T-Lymphocytes - immunology; CD8; CD8-Positive T-Lymphocytes - immunology; COVID-19; COVID-19 - immunology; COVID-19 Vaccines; Female; Humans; Male; Middle Aged; SARS-CoV-2; SARS-CoV-2 - immunology; SARS-CoV-2 - metabolism; Spike Glycoprotein, Coronavirus - immunology; T cells; vaccines; VOCs; Young Adult
• ISSN: 2666-3791; 2666-3791
• DOI: 10.1016/j.xcrm.2021.100355

The emergence of SARS-CoV-2 variants with evidence of antibody escape highlight the importance of addressing whether the total CD4+ and CD8+ T cell recognition is also affected. Here, we compare SARS-CoV-2-specific CD4+ and CD8+ T cells against the B.1.1.7, B.1.351, P.1, and CAL.20C lineages in COVID-19 convalescents and in recipients of the Moderna (mRNA-1273) or Pfizer/BioNTech (BNT162b2) COVID-19 vaccines. The total reactivity against SARS-CoV-2 variants is similar in terms of magnitude and frequency of response, with decreases in the 10%–22% range observed in some assay/VOC combinations. A total of 7% and 3% of previously identified CD4+ and CD8+ T cell epitopes, respectively, are affected by mutations in the various VOCs. Thus, the SARS-CoV-2 variants analyzed here do not significantly disrupt the total SARS-CoV-2 T cell reactivity; however, the decreases observed highlight the importance for active monitoring of T cell reactivity in the context of SARS-CoV-2 evolution. [Display omitted] T cells of exposed donors or vaccinees effectively recognize SARS-CoV-2 variantsEffective recognition in AIM and FluoroSPOT assays, for spike and other proteins93% and 97% of CD4 and CD8 epitopes are 100% conserved across variants Tarke et al. show that SARS-CoV-2-specific memory CD4 and CD8 T cells exposed to the ancestral strain by infection or vaccination effectively recognize the variants B.1.1.7, B.1.351, P.1, and CAL.20C. The majority of T cell epitopes are unaffected by mutations in these variant strains.