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

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.

• Autores: Castaño Monsalve, Diana María; Laczkó, Dorottya; Hogan, Michael J.; Toulmin, Sushila A.; Hicks, Philip; Lederer, Katlyn; Gaudette, Brian T.; Amanat, Fatima; Muramatsu, Hiromi; Oguin III, 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; LoccII, Michela; Pardi, Norbert
• Tipo de recurso: Article of investigation
• Fecha de publicación: 2020
• Institución: Universidad de Antioquia
• Repositorio: Repositorio UdeA
• Idioma: eng
• OAI Identifier: oai:bibliotecadigital.udea.edu.co:10495/42022
• Acceso en línea: https://hdl.handle.net/10495/42022
• Palabra clave: COVID-19; Anticuerpos Neutralizantes; Antibodies, Neutralizing; Antígenos Virales; Antigens, Viral; Linfocitos B; B-Lymphocytes; Vacunas de ARNm; mRNA Vaccines; Betacoronavirus; Linfocitos T CD4-Positivos; CD4-Positive T-Lymphocytes; Linfocitos T CD8-positivos; CD8-Positive T-Lymphocytes; Vacunas contra la COVID-19; COVID-19 Vaccines; Infecciones por Coronavirus; Coronavirus Infections; Modelos Animales de Enfermedad; Disease Models, Animal; Furina; Furin; Inmunidad Humoral; Immunity, Humoral; Inmunogenicidad Vacunal; Immunogenicity, Vaccine; SARS-CoV-2; Activación de Linfocitos; Lymphocyte Activation; Pandemias; Pandemics; Neumonía Viral; Pneumonia, Viral; Glicoproteína de la Espiga del Coronavirus; Spike Glycoprotein, Coronavirus; https://id.nlm.nih.gov/mesh/D000086382; https://id.nlm.nih.gov/mesh/D057134; https://id.nlm.nih.gov/mesh/D000956; https://id.nlm.nih.gov/mesh/D002478; https://id.nlm.nih.gov/mesh/D000087503; https://id.nlm.nih.gov/mesh/D000073640; https://id.nlm.nih.gov/mesh/D015496; https://id.nlm.nih.gov/mesh/D018414; https://id.nlm.nih.gov/mesh/D000086663; https://id.nlm.nih.gov/mesh/D018352; https://id.nlm.nih.gov/mesh/D004195; https://id.nlm.nih.gov/mesh/D045683; https://id.nlm.nih.gov/mesh/D056724; https://id.nlm.nih.gov/mesh/D000071497; https://id.nlm.nih.gov/mesh/D000086402; https://id.nlm.nih.gov/mesh/D008213; https://id.nlm.nih.gov/mesh/D058873; https://id.nlm.nih.gov/mesh/D011024; https://id.nlm.nih.gov/mesh/D064370
• Rights: openAccess
• License: https://creativecommons.org/licenses/by-nc-nd/2.5/co/