mRNA-LNP vaccine-induced CD8(+) T cells protect mice from lethal SARS-CoV-2 infection in the absence of specific antibodies.

The role of CD8(+) T cells in SARS-CoV-2 pathogenesis or mRNA-LNP vaccine-induced protection from lethal COVID-19 is unclear. Using mouse-adapted SARS-CoV-2 virus (MA30) in C57BL/6 mice, we show that CD8(+) T cells are unnecessary for the intrinsic resistance of female or the susceptibility of male mice to lethal SARS-CoV-2 infection. Also, mice immunized with a di-proline prefusion-stabilized full-length SARS-CoV-2 Spike (S-2P) mRNA-LNP vaccine, which induces Spike-specific antibodies and CD8(+) T cells specific for the Spike-derived VNFNFNGL peptide, are protected from SARS-CoV-2 infection-induced lethality and weight loss, while mice vaccinated with mRNA-LNPs encoding only VNFNFNGL are protected from lethality but not weight loss. CD8(+) T cell depletion ablates protection in VNFNFNGL but not in S-2P mRNA-LNP-vaccinated mice. Therefore, mRNA-LNP vaccine-induced CD8(+) T cells are dispensable when protective antibodies are present but essential for survival in their absence. Hence, vaccine-induced CD8(+) T cells may be critical to protect against SARS-CoV-2 variants that mutate epitopes targeted by protective antibodies.