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

Montoya, Brian and Melo-Silva, Carolina R. and Tang, Lingjuan and Kafle, Samita and Lidskiy, Peter and Bajusz, Csaba and Vadovics, Mate and Muramatsu, Hiromi and Ábrahám, Edit and Lipinszki, Zoltán and Chatterjee, Debotri and Scher, Gabrielle and Benitez, Juliana and Sung, Molly M. H. and Tam, Ying K. and Catanzaro, Nicholas J. and Schaefer, Alexandra and Andino, Raul and Baric, Ralph S. and Martinez, David R. and Pardi, Norbert and Sigal, Luis J. (2024) mRNA-LNP vaccine-induced CD8+T cells protect mice from lethal SARS-CoV-2 infection in the absence of specific antibodies. MOLECULAR THERAPY, 32 (6). pp. 1790-1804. ISSN 1525-0016

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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 SARSCoV-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 mRNApresent but essential for survival in their absence. Hence, vacSARS-CoV-2 variants that mutate epitopes targeted by protective antibodies.

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