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- Title
A pan-variant mRNA-LNP T cell vaccine protects HLA transgenic mice from mortality after infection with SARS-CoV-2 Beta.
- Authors
Carter, Brandon; Pinghan Huang; Ge Liu; Yuejin Liang; Lin, Paulo J. C.; Bi-Hung Peng; McKay, Lindsay G. A.; Dimitrakakis, Alexander; Hsu, Jason; Tat, Vivian; Saenkham-Huntsinger, Panatda; Jinjin Chen; Kaseke, Clarety; Gaiha, Gaurav D.; Qiaobing Xu; Griffiths, Anthony; Tam, Ying K.; Tseng, Chien-Te K.; Gifford, David K.
- Abstract
Licensed COVID-19 vaccines ameliorate viral infection by inducing production of neutralizing antibodies that bind the SARS-CoV-2 Spike protein and inhibit viral cellular entry. However, the clinical effectiveness of these vaccines is transitory as viral variants escape antibody neutralization. Effective vaccines that solely rely upon a T cell response to combat SARS-CoV-2 infection could be transformational because they can utilize highly conserved short pan-variant peptide epitopes, but a mRNA-LNP T cell vaccine has not been shown to provide effective anti-SARS-CoV-2 prophylaxis. Here we show a mRNA-LNP vaccine (MIT-T-COVID) based on highly conserved short peptide epitopes activates CD8+ and CD4+ T cell responses that attenuate morbidity and prevent mortality in HLA-A*02:01 transgenic mice infected with SARS-CoV-2 Beta (B.1.351). We found CD8+ T cells in mice immunized with MIT-T-COVID vaccine significantly increased from 1.1% to 24.0% of total pulmonary nucleated cells prior to and at 7 days post infection (dpi), respectively, indicating dynamic recruitment of circulating specific T cells into the infected lungs. Mice immunized with MIT-T-COVID had 2.8 (2 dpi) and 3.3 (7 dpi) times more lung infiltrating CD8+ T cells than unimmunized mice. Mice immunized with MIT-T-COVID had 17.4 times more lung infiltrating CD4+ T cells than unimmunized mice (7 dpi). The undetectable specific antibody response in MIT-T-COVID-immunized mice demonstrates specific T cell responses alone can effectively attenuate the pathogenesis of SARS-CoV-2 infection. Our results suggest further study is merited for pan-variant T cell vaccines, including for individuals that cannot produce neutralizing antibodies or to help mitigate Long COVID.
- Subjects
T cells; TRANSGENIC mice; POST-acute COVID-19 syndrome; SARS-CoV-2; VACCINE effectiveness
- Publication
Frontiers in Immunology, 2023, Vol 14, p1
- ISSN
1664-3224
- Publication type
Article
- DOI
10.3389/fimmu.2023.1135815