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 3rd ,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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