NVX-CoV2373 vaccination induces functional SARS-CoV-2–specific CD4 ⁺ and CD8 ⁺ T cell responses

NVX-CoV2373 is an adjuvanted recombinant full-length SARS-CoV-2 spike trimer protein vaccine demonstrated to be protective against COVID-19 in efficacy trials. Here we demonstrate that vaccinated subjects made CD4 ⁺ T cell responses after one and two doses of NVX-CoV2373, and a subset of individuals made CD8 ⁺ T cell responses. Characterization of the vaccine-elicited CD8 ⁺ T cells demonstrated IFN γ production. Characterization of the vaccine-elicited CD4 ⁺ T cells revealed both circulating T follicular helper cells (cT _FH ) and T _H 1 cells (IFN γ , TNFα, and IL-2) were detectable within 7 days of the primary immunization. Spike-specific CD4 ⁺ T cells were correlated with the magnitude of the later SARS-CoV-2 neutralizing antibody titers, indicating that robust generation of CD4 ⁺ T cells, capable of supporting humoral immune responses, may be a key characteristic of NVX-CoV2373 which utilizes Matrix-M™ adjuvant.