Protective activity of mRNA vaccines against ancestral and variant SARS-CoV-2 strains

Baoling Ying, Bradley Whitener, Laura A. VanBlargan, Ahmed O. Hassan, Swathi Shrihari, Chieh Yu Liang, Courtney E. Karl, Samantha Mackin, Rita E. Chen, Natasha M. Kafai, Samuel H. Wilks, Derek J. Smith, Juan Manuel Carreño, Gagandeep Singh, Florian Krammer, Andrea Carfi, Sayda M. Elbashir, Darin K. Edwards, Larissa B. Thackray, Michael Diamond

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


Although mRNA vaccines encoding the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prevent COVID-19, the emergence of new viral variants jeopardizes 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 after mRNA vaccination, breakthrough infection and disease may occur with some SARS-CoV-2 variants.

Original languageEnglish
Article numbereabm3302
JournalScience translational medicine
Issue number630
StatePublished - Feb 2 2022


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