A Single Immunization with Nucleoside-Modified mRNA Vaccines Elicits Strong Cellular and Humoral Immune Responses against SARS-CoV-2 in Mice

单次接种核苷修饰的mRNA疫苗即可在小鼠体内诱导针对SARS-CoV-2的强效细胞和体液免疫反应

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作者:Dorottya Laczkó,Michael J Hogan,Sushila A Toulmin,Philip Hicks,Katlyn Lederer,Brian T Gaudette,Diana Castaño,Fatima Amanat,Hiromi Muramatsu,Thomas H Oguin rd,Amrita Ojha,Lizhou Zhang,Zekun Mu,Robert Parks,Tomaz B Manzoni,Brianne Roper,Shirin Strohmeier,István Tombácz,Leslee Arwood,Raffael Nachbagauer,Katalin Karikó,Jack Greenhouse,Laurent Pessaint,Maciel Porto,Tammy Putman-Taylor,Amanda Strasbaugh,Tracey-Ann Campbell,Paulo J C Lin,Ying K Tam,Gregory D Sempowski,Michael Farzan,Hyeryun Choe,Kevin O Saunders,Barton F Haynes,Hanne Andersen,Laurence C Eisenlohr,Drew Weissman,Florian Krammer,Paul Bates,David Allman,Michela Locci,Norbert Pardi

Abstract

SARS-CoV-2 infection has emerged as a serious global pandemic. Because of the high transmissibility of the virus and the high rate of morbidity and mortality associated with COVID-19, developing effective and safe vaccines is a top research priority. Here, we provide a detailed evaluation of the immunogenicity of lipid nanoparticle-encapsulated, nucleoside-modified mRNA (mRNA-LNP) vaccines encoding the full-length SARS-CoV-2 spike protein or the spike receptor binding domain in mice. We demonstrate that a single dose of these vaccines induces strong type 1 CD4+ and CD8+ T cell responses, as well as long-lived plasma and memory B cell responses. Additionally, we detect robust and sustained neutralizing antibody responses and the antibodies elicited by nucleoside-modified mRNA vaccines do not show antibody-dependent enhancement of infection in vitro. Our findings suggest that the nucleoside-modified mRNA-LNP vaccine platform can induce robust immune responses and is a promising candidate to combat COVID-19.

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