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.

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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