A pan-variant mRNA-LNP T cell vaccine protects HLA transgenic mice from mortality after infection with SARS-CoV-2 Beta

Frontiers in Immunology

Immunology

Paulo J. C. Lin¹  Ying K. Tam¹  Alexander Dimitrakakis²  Ge Liu²  Brandon Carter²  David K. Gifford³  Qiaobing Xu⁴  Jinjin Chen⁴  Pinghan Huang⁵  Yuejin Liang⁵  Panatda Saenkham-Huntsinger⁵  Chien-Te K. Tseng⁶  Jason Hsu⁷  Bi-Hung Peng⁷  Vivian Tat⁸  Anthony Griffiths⁹  Lindsay G. A. McKay⁹  Clarety Kaseke^1,10  Gaurav D. Gaiha^1,11 

[1] Acuitas Therapeutics, Vancouver, BC, Canada;Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA, United States;Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA, United States;Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA, United States;Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA, United States;Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, United States;Department of Biomedical Engineering, Tufts University, Medford, MA, United States;Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, TX, United States;Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, TX, United States;Department of Neuroscience, Cell Biology, and Anatomy, The University of Texas Medical Branch, Galveston, TX, United States;Department of Pathology, The University of Texas Medical Branch, Galveston, TX, United States;Department of Neuroscience, Cell Biology, and Anatomy, The University of Texas Medical Branch, Galveston, TX, United States;Department of Pathology, The University of Texas Medical Branch, Galveston, TX, United States;National Emerging Infectious Diseases Laboratories, Department of Microbiology, Boston University School of Medicine, Boston, MA, United States;Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, United States;Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, United States;Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, United States;

关键词: COVID-19;    SARS-CoV-2;    peptide vaccine;    mRNA-LNP;    challenge study;    T cell vaccine;   

DOI  :  10.3389/fimmu.2023.1135815

 received in 2023-01-01, accepted in 2023-02-06,  发布年份 2023

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

Unknown   
Copyright © 2023 Carter, Huang, Liu, Liang, Lin, Peng, McKay, Dimitrakakis, Hsu, Tat, Saenkham-Huntsinger, Chen, Kaseke, Gaiha, Xu, Griffiths, Tam, Tseng and Gifford