A single immunization with nucleoside-modified mRNA vaccines elicits strong cellular and humoral immune responses against SARS-CoV-2 in mice

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

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.