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

Abstract	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.
Authors	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 S Diamond
Journal	Science translational medicine (Sci Transl Med) Vol. 14 Issue 630 Pg. eabm3302 (Feb 02 2022) ISSN: 1946-6242 [Electronic] United States
PMID	34846168 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References	Antibodies, Neutralizing Antibodies, Viral COVID-19 Vaccines Spike Glycoprotein, Coronavirus Vaccines, Synthetic mRNA Vaccines
Topics	Animals Antibodies, Neutralizing Antibodies, Viral COVID-19 COVID-19 Vaccines Humans Mice SARS-CoV-2 Spike Glycoprotein, Coronavirus (genetics) Vaccines, Synthetic mRNA Vaccines

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