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

• Published in: Immunity (Cambridge, Mass.) Vol. 53; no. 4; pp. 724 - 732.e7
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 13.10.2020; Elsevier Limited; Cell Press
• Subjects: Animals; Antibodies; Antibodies, Neutralizing - biosynthesis; Antibodies, Viral - biosynthesis; Antigens; B-Lymphocytes - drug effects; B-Lymphocytes - immunology; B-Lymphocytes - virology; Betacoronavirus - drug effects; Betacoronavirus - immunology; Betacoronavirus - pathogenicity; CD4 antigen; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - virology; CD8 antigen; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - virology; Coronavirus Infections - genetics; Coronavirus Infections - immunology; Coronavirus Infections - pathology; Coronavirus Infections - prevention & control; Coronaviruses; COVID-19; COVID-19 Vaccines; Design; Disease Models, Animal; Furin - genetics; Furin - immunology; Humans; Immune response; Immune response (humoral); Immunity, Humoral - drug effects; Immunization; Immunization - methods; Immunogenicity; Immunogenicity, Vaccine; Immunologic Memory - drug effects; Immunological memory; Infections; Lipids; Lungs; Lymphocyte Activation - drug effects; Lymphocytes; Lymphocytes T; Memory cells; Mice; Mice, Inbred BALB C; Morbidity; mRNA; mRNA vaccine; mRNA vaccines; mRNA-LNP; Nanoparticles; Nanoparticles - administration & dosage; Nanoparticles - chemistry; nucleoside-modified mRNA; Nucleosides; Pandemics; Pandemics - prevention & control; Plasma; Pneumonia, Viral - immunology; Pneumonia, Viral - pathology; Pneumonia, Viral - prevention & control; Proteins; RNA, Messenger - genetics; RNA, Messenger - immunology; RNA, Viral - genetics; RNA, Viral - immunology; Robustness; SARS-CoV-2; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus - genetics; Spike Glycoprotein, Coronavirus - immunology; Spike protein; Spleen; Tumor necrosis factor-TNF; Vaccines; Vaccines, Synthetic; Viral diseases; Viral Vaccines - administration & dosage; Viral Vaccines - biosynthesis; Viral Vaccines - genetics; Viruses; Zika virus; COVID-19; SARS-CoV-2; nucleoside-modified mRNA; mRNA-LNP; mRNA vaccine
• ISSN: 1074-7613; 1097-4180; 1097-4180
• DOI: 10.1016/j.immuni.2020.07.019

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. [Display omitted] •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 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.