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Synthesis and Characterization of mRNA-Loaded PolyBeta Aminoesters Nanoparticles for Vaccination Purposes
Published on: August 13, 2021
Protective activity of mRNA vaccines against ancestral and variant SARS-CoV-2 strains
Baoling Ying1, Bradley Whitener1, Laura A VanBlargan1
1Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Abstract:
Although mRNA vaccines prevent COVID-19, variants jeopardize their efficacy as immunity wanes. Here, we assessed the immunogenicity and protective activity of historical (mRNA-1273, designed for Wuhan-1 spike) or modified (mRNA-1273.351, designed for B.1.351 spike) preclinical Moderna mRNA vaccines in 129S2 and K18-hACE2 mice. Immunization with high or low dose formulations of mRNA vaccines induced neutralizing antibodies in serum against ancestral SARS-CoV-2 and several variants, although levels were lower particularly 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. Nonetheless, low-dose formulations of the vaccines, which produced lower magnitude antibody and T cell responses, and serve as a possible model for waning immunity, showed breakthrough lung infection and pneumonia with B.1.617.2. Thus, as levels of immunity induced by mRNA vaccines decline, breakthrough infection and disease likely will occur with some SARS-CoV-2 variants, suggesting a need for additional booster regimens.
Insights
mRNA vaccines offer COVID-19 protection, but waning immunity and variants like Delta can lead to breakthrough infections. Booster shots may be needed to maintain protection against SARS-CoV-2 variants.
Area of Science:
- Immunology
- Vaccinology
- Virology
Background:
- Waning immunity and emerging SARS-CoV-2 variants challenge the long-term efficacy of mRNA vaccines.
- Assessing vaccine effectiveness against diverse viral strains and declining immune responses is crucial.
Approach:
- Evaluated historical (mRNA-1273) and modified (mRNA-1273.351) Moderna mRNA vaccines in mouse models (129S2 and K18-hACE2).
- Assessed immunogenicity (neutralizing antibodies, T cell responses) and protective activity against ancestral and variant SARS-CoV-2 strains.
- Investigated effects of high and low vaccine doses, simulating waning immunity.
Key Points:
- Both vaccine formulations induced neutralizing antibodies against SARS-CoV-2 variants, though responses were lower against the Delta variant.
- High-dose vaccines provided protection against weight loss and lung pathology across all tested viruses.
- Low-dose vaccines, mimicking waning immunity, showed breakthrough infections and pneumonia with the Delta variant.
Conclusions:
- Declining mRNA vaccine immunity may increase susceptibility to breakthrough infections and disease with certain SARS-CoV-2 variants.
- The findings underscore the potential need for additional booster immunizations to sustain protection.
- Further research into variant-specific vaccine efficacy and optimal boosting strategies is warranted.
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