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

单次核苷修饰的 mRNA 疫苗免疫小鼠即可引发针对 SARS-CoV-2 的强烈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 3rd, Amrita Ojha, Lizhou Zhang, Zekun Mu, Robert Parks, Tomaz B Manzoni, Brianne Roper, Shirin Strohmeier, István Tombácz, Leslee Arwood

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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