Systematic examination of T cell responses to SARS-CoV-2 versus influenza virus reveals distinct inflammatory profile

Abstract

There is a pressing need for an in-depth understanding of immunity to SARS-CoV-2. Here we investigated T cell recall responses to fully glycosylated Spike trimer, recombinant N protein as well as to S, N, M and E peptide pools in the early convalescent phase. All subjects showed SARS-CoV-2-specific T cell responses to at least one antigen. SARS-CoV-2-specific CD4+ T cells were primarily of the central memory phenotype and exhibited a lower IFN-[gamma] to TNF-[alpha] ratio compared to influenza-specific responses of the same donors, independent of disease severity. SARS-CoV-2-specific T cells were less multifunctional than influenza-specific T cells, particularly in severe cases, potentially suggesting exhaustion. High IL-10 production was noted in response to N protein, possibly contributing to immunosuppression, with potential implications for vaccine design. We observed granzyme B+/IFN-[gamma] CD4+ and CD8+ proliferative responses to peptide pools in most individuals, with CD4+ responses predominating over CD8+ responses. Peripheral T follicular helper responses to S or N strongly correlated with serum neutralization assays as well as RBD-specific IgA. Overall, T cell responses to SARS-CoV-2 are robust, however, CD4+ Th1 responses predominate over CD8+ responses and are more inflammatory with a weaker Tfh response than influenza-specific CD4+ responses, potentially contributing to COVID-19 disease.

COVID-19 vaccine mRNA-1273 elicits a protective immune profile in mice that is not associated with vaccine-enhanced disease upon SARS-CoV-2 challenge

“…During natural SARS-CoV-2 infection, IFNg does not appear to strongly dominate the S-specific Th1 CD4 + cell profile over IL-2 and TNFa, and SARS-CoV-2 may not polarize as strongly toward the type 1 signature as influenza (Braun et al, 2020;Law et al, 2021;Peng et al, 2020;Sekine et al, 2020). A similar pattern of cytokine expression is also observed following human vaccination with mRNA-1273 (Jackson et al, 2020) and a recombinant spike protein nanoparticle vaccine (NVX-CoV2373; Keech et al, 2020).…”