mRNA-LNP vaccine-induced CD8+ T cells protect mice from lethal SARS-CoV-2 infection in the absence of specific antibodies
Brian Montoya, Carolina R. Melo‐Silva, Lingjuan Tang, Samita Kafle, Peter Lidskiy, Csaba Bajusz, Máté Vadovics, Hiromi Muramatsu, Edit Ábrahám, Zoltán Lipinszki, Debotri Chatterjee, Gabrielle Scher, J.M. López Benítez, Molly M. H. Sung, Ying K. Tam, Nicholas J Catanzaro, Alexandra Schäfer, Raul Andino, Ralph S. Baric, David R. Martinez, Norbert Pardi, Luis J. Sigal
Abstract
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.