Description mRNA-1273-based vaccines protect against historical and variant SARS-CoV-2 strains in 129S2 and K18-hACE2 mice. Although mRNA vaccines encoding the spike protein of SARS-CoV-2 prevent COVID-19, the emergence of new viral variants jeopardize their efficacy. Here, we assessed the immunogenicity and protective activity of historical (mRNA-1273, designed for Wuhan-1 spike protein) or modified (mRNA-1273.351, designed for B.1.351 spike protein) Moderna mRNA vaccines in 129S2 and K18-hACE2 mice. Mice were immunized with either high-dose or low-dose formulations of the mRNA vaccines, where low-dose vaccination modeled suboptimal immune responses. Immunization with formulations at either dose induced neutralizing antibodies in serum against ancestral SARS-CoV-2 WA1/2020 and several virus variants, although serum titers were lower against the B.1.617.2 (Delta) virus. Protection against weight loss and lung pathology was observed with all high-dose vaccines against all viruses. However, low-dose formulations of the vaccines, which produced lower magnitude antibody and T cell responses, showed breakthrough lung infections with B.1.617.2 and development of pneumonia in K18-hACE2 mice. Thus, in individuals with reduced immunity following mRNA vaccination, breakthrough infection and disease may occur with some SARS-CoV-2 variants.
【초록키워드】 COVID-19, viruses, neutralizing antibody, SARS-CoV-2, mRNA vaccination, Efficacy, Vaccine, vaccination, Immunity, Vaccines, Pneumonia, antibody, mRNA vaccine, B.1.351, mRNA-1273, protection, variant, Delta, B.1.617.2, Lung infection, virus, Spike protein, mRNA vaccines, serum, SARS-CoV-2 variants, immune responses, low-dose, T cell responses, K18-hACE2 mice, Breakthrough infection, virus variants, viral variant, disease, Protective, Lung pathology, dose, weight loss, High-dose, individual, description, SARS-CoV-2 strain, serum titer, Prevent, immunized, Wuhan-1, SARS-CoV-2 WA1/2020, mRNA-1273.351, PROTECT, Moderna mRNA vaccine, produced, reduced, occur, the spike protein, magnitude, 【제목키워드】 mRNA vaccine, variant, SARS-CoV-2 strain,