Protective activity of mRNA vaccines against ancestral and variant SARS-CoV-2 strains
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- Baoling Ying
- Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
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- Bradley Whitener
- Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
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- Laura A. VanBlargan
- Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
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- Ahmed O. Hassan
- Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
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- Swathi Shrihari
- Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
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- Chieh-Yu Liang
- Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
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- Courtney E. Karl
- Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
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- Samantha Mackin
- Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
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- Rita E. Chen
- Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
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- Natasha M. Kafai
- Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
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- Samuel H. Wilks
- Center for Pathogen Evolution, Department of Zoology, University of Cambridge, Cambridge CB2 3EJ, UK.
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- Derek J. Smith
- Center for Pathogen Evolution, Department of Zoology, University of Cambridge, Cambridge CB2 3EJ, UK.
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- Juan Manuel Carreño
- Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
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- Gagandeep Singh
- Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
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- Florian Krammer
- Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
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- Andrea Carfi
- Moderna Inc., Cambridge, MA 02139, USA.
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- Sayda M. Elbashir
- Moderna Inc., Cambridge, MA 02139, USA.
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- Darin K. Edwards
- Moderna Inc., Cambridge, MA 02139, USA.
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- Larissa B. Thackray
- Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
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- Michael S. Diamond
- Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
書誌事項
- 公開日
- 2022-02-02
- DOI
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- 10.1126/scitranslmed.abm3302
- 公開者
- American Association for the Advancement of Science (AAAS)
この論文をさがす
説明
<jats:p>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.</jats:p>
収録刊行物
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- Science Translational Medicine
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Science Translational Medicine 14 (630), eabm3302-, 2022-02-02
American Association for the Advancement of Science (AAAS)
