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

Authors :
Lizhou Zhang
Maciel Porto
Norbert Pardi
Katalin Karikó
Gregory D. Sempowski
Brian T. Gaudette
Sushila A. Toulmin
Hyeryun Choe
Tracey Ann Campbell
Tammy Putman-Taylor
Leslee Arwood
Barton F. Haynes
Michael Farzan
Katlyn Lederer
Kevin O. Saunders
Hanne Leth Andersen
Florian Krammer
Paul Bates
Brianne Roper
Laurent Pessaint
Dorottya Laczkó
Amanda Strasbaugh
Thomas H. Oguin
Jack Greenhouse
Diana Castaño
Michael J. Hogan
Fatima Amanat
Shirin Strohmeier
Laurence C. Eisenlohr
Amrita Ojha
Michela Locci
Raffael Nachbagauer
David Allman
István Tombácz
Tomaz B. Manzoni
Robert Parks
Paulo J.C. Lin
Zekun Mu
Drew Weissman
Hiromi Muramatsu
Philip Hicks
Ying K. Tam
Source :
Immunity
Publication Year :
2020
Publisher :
Elsevier BV, 2020.

Abstract

Summary 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.<br />Highlights • mRNA vaccines induce robust type 1 CD4+ and CD8+ T cells in the spleen and lung • Vaccine-induced T cells readily exit the vasculature and enter the lung parenchyma • mRNA vaccines elicit strong long-lived plasma cell and memory B cell responses • mRNA vaccines induce antibodies with potent anti-SARS-CoV-2 neutralization activity<br />SARS-CoV-2 mRNA-based vaccines are among the most promising vaccine candidates against COVID-19. Laczkó et al. evaluate two nucleoside-modified mRNA vaccine candidates in mice and demonstrate that they induce potent T and B cell immune responses and high levels of neutralizing antibodies after administration of a single vaccine dose.

Details

Language :
English
ISSN :
10747613
Database :
OpenAIRE
Journal :
Immunity
Accession number :
edsair.doi.dedup.....d81d18b05ab82aa2cb41667addede581
Full Text :
https://doi.org/10.1016/j.immuni.2020.07.019