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

被引：6

作者：

Montoya, Brian ^{[1
]}

Melo-Silva, Carolina R. ^{[1
]}

Tang, Lingjuan ^{[1
]}

Kafle, Samita ^{[1
]}

Lidskiy, Peter ^{[2
]}

Bajusz, Csaba ^{[3
,4
]}

Vadovics, Mate ^{[3
]}

Muramatsu, Hiromi ^{[3
]}

Abraham, Edit ^{[4
,5
]}

Lipinszki, Zoltan ^{[4
,5
]}

Chatterjee, Debotri ^{[6
]}

Scher, Gabrielle ^{[1
]}

Benitez, Juliana ^{[1
]}

Sung, Molly M. H. ^{[7
]}

Tam, Ying K. ^{[7
]}

Catanzaro, Nicholas J. ^{[8
]}

Schaefer, Alexandra ^{[8
]}

Andino, Raul ^{[2
]}

Baric, Ralph S. ^{[8
]}

Martinez, David R. ^{[9
]}

Pardi, Norbert ^{[3
]}

Sigal, Luis J. ^{[1
]}

机构：

[1] Thomas Jefferson Univ, Dept Microbiol & Immunol, Bluemle Life Sci Bldg, Philadelphia, PA 19107 USA

[2] Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94158 USA

[3] Univ Penn, Perelman Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA

[4] HUN REN Biol Res Ctr, Inst Genet, Natl Lab Biotechnol, H-6726 Szeged, Hungary

[5] REN Biol Res Ctr, Inst Biochem, Synthet & Syst Biol Unit, MTA SZBK Lendulet Lab Cell Cycle Regulat, Szeged, Hungary

[6] Thomas Jefferson Univ Vickie, Jack Farber Inst Neurosci, Dept Neurosci, Philadelphia, PA USA

[7] Acuitas Therapeut, Vancouver, BC V6T 1Z3, Canada

[8] Univ North Carolina Chapel Hill, Dept Epidemiol, Microbiol & Immunol, Chapel Hill, NC 27599 USA

[9] Yale Sch Med, Ctr Infect & Immun, Dept Immunobiol, New Haven, CT 06520 USA

来源：

MOLECULAR THERAPY | 2024年 / 32卷 / 06期

关键词：

CD8(+) T-CELLS; MHC CLASS-I; LIPID NANOPARTICLES; MEMORY; IMMUNOGENICITY; IDENTIFICATION; EXPRESSION; RESPONSES; EFFECTOR; EPITOPES;

D O I：

10.1016/j.ymthe.2024.04.019

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

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.

引用

页码：1790 / 1804

页数：15

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