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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.

Science Translational Medicine
|November 30, 2021
PubMed

Insights

mRNA vaccines offer protection against COVID-19, but variants may reduce efficacy. Low-dose vaccination in mice showed reduced antibody responses, leading to breakthrough infections with the Delta variant.

Area of Science:

  • Immunology
  • Virology
  • Vaccinology

Background:

  • Emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants pose a threat to the effectiveness of existing mRNA vaccines.
  • Current mRNA vaccines target the ancestral Wuhan-1 strain's spike protein, necessitating evaluation against new variants.

Purpose of the Study:

  • To assess the immunogenicity and protective efficacy of historical (mRNA-1273) and modified (mRNA-1273.351) Moderna mRNA vaccines against SARS-CoV-2 variants.
  • To model suboptimal immune responses using low-dose vaccination in mice.

Main Methods:

  • Immunization of 129S2 and K18-hACE2 mice with high-dose or low-dose formulations of mRNA-1273 and mRNA-1273.351 vaccines.
  • Measurement of neutralizing antibody titers against ancestral and variant SARS-CoV-2 strains.
  • Assessment of protection against weight loss and lung pathology post-challenge with SARS-CoV-2 variants.

Main Results:

  • Both vaccine formulations induced neutralizing antibodies against ancestral SARS-CoV-2 and several variants, with lower titers against the Delta (B.1.617.2) variant.
  • High-dose vaccination provided protection against weight loss and lung pathology for all tested viruses.
  • Low-dose vaccination resulted in lower antibody and T cell responses, leading to breakthrough lung infections and pneumonia with the Delta variant in K18-hACE2 mice.

Conclusions:

  • mRNA vaccines elicit neutralizing antibodies against SARS-CoV-2 variants, but efficacy may be reduced against certain strains like Delta.
  • Suboptimal immune responses following mRNA vaccination can lead to breakthrough infections and disease with emerging SARS-CoV-2 variants.

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