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- Title
Protective activity of mRNA vaccines against ancestral and variant SARS-CoV-2 strains.
- Authors
Ying, Baoling; Whitener, Bradley; VanBlargan, Laura A.; Hassan, Ahmed O.; Shrihari, Swathi; Liang, Chieh-Yu; Karl, Courtney E.; Mackin, Samantha; Chen, Rita E.; Kafai, Natasha M.; Wilks, Samuel H.; Smith, Derek J.; Carreño, Juan Manuel; Singh, Gagandeep; Krammer, Florian; Carfi, Andrea; Elbashir, Sayda M.; Edwards, Darin K.; Thackray, Larissa B.; Diamond, Michael S.
- 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. A variant vaccine: The success of mRNA vaccines against SARS-CoV-2 is being challenged by the emergence of variants of concern (VOC). To address this, it may be necessary to develop vaccines that encode spike proteins from these VOC. Here, Ying et al. compared two SARS-CoV-2 mRNA vaccines, the mRNA-1273 vaccine, which is now in use globally, and a variant version, mRNA-1273.351. The authors showed that mRNA-1273, mRNA-1273.351, and a mix of the two, mRNA-1273.211, conferred protection against SARS-CoV-2 in two different mouse models when administered at a higher dose. Both vaccines also conferred some degree of protection at a lower dose of vaccine, which the authors use to recapitulate suboptimal vaccine responses. Together, these results support the continued development of mRNA vaccines for SARS-CoV-2.
- Subjects
WUHAN (China); SARS-CoV-2; VIRAL antibodies; COVID-19 vaccines; VACCINES; MESSENGER RNA; BREAKTHROUGH infections
- Publication
Science Translational Medicine, 2022, Vol 14, Issue 630, p1
- ISSN
1946-6234
- Publication type
Article
- DOI
10.1126/scitranslmed.abm3302