The spread of the SARS-CoV-2 into a global pandemic within a few months of onset motivates the development of a rapidly scalable vaccine. Here, we present a self-amplifying RNA encoding the SARS-CoV-2 spike protein encapsulated within a lipid nanoparticle (LNP) as a vaccine. We observe remarkably high and dose-dependent SARS-CoV-2 specific antibody titers in mouse sera, as well as robust neutralization of both a pseudo-virus and wild-type virus. Upon further characterization we find that the neutralization is proportional to the quantity of specific IgG and of higher magnitude than recovered COVID-19 patients. saRNA LNP immunizations induce a Th1-biased response in mice, and there is no antibody-dependent enhancement (ADE) observed. Finally, we observe high cellular responses, as characterized by IFN- γ production, upon re-stimulation with SARS-CoV-2 peptides. These data provide insight into the vaccine design and evaluation of immunogenicity to enable rapid translation to the clinic. Here, the authors develop a self-amplifying RNA encoding the SARS-CoV-2 spike protein encapsulated within a lipid nanoparticle as a vaccine candidate and show induction of neutralization antibody titers in mice that are comparable to titers in convalescent sera of patients.
【저자키워드】 Molecular medicine, RNA vaccines, Biomaterials - vaccines, 【초록키워드】 SARS-CoV-2, IgG, Vaccine, translation, Antibody-dependent enhancement, neutralization, SARS-CoV-2 peptides, immunization, LNP, Spike protein, RNA, global pandemic, Spread, mice, sera, Antibody titer, vaccine candidate, IFN, ADE, patients, convalescent sera, Recovered COVID-19 patients, Cellular responses, wild-type virus, pseudo-virus, robust, observé, develop, characterized, magnitude, induce, comparable, dose-dependent, the vaccine, the SARS-CoV-2, 【제목키워드】 SARS-CoV-2, RNA, mice, vaccine candidate, Neutralizing antibody titer, induce,