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Pre-existing immunity modulates responses to mRNA boosters.

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Area of Science:

  • Immunology
  • Vaccinology
  • Virology

Background:

  • mRNA vaccines (mRNA-1273, BNT162b2) are effective against severe COVID-19 but boosters are needed due to breakthrough infections, variants, and waning immunity.
  • The impact of pre-existing immunity on the efficacy of mRNA vaccine boosters is not fully understood.

Approach:

  • Analyzed antibody levels in individuals receiving mRNA boosters after initial vaccination.
  • Conducted mechanistic studies in mice to investigate the effects of pre-existing antibodies on mRNA vaccination responses.
  • Evaluated the comparative effectiveness of updated Omicron vaccines versus original vaccines based on host serostatus.

Key Points:

  • Lower pre-boost antibody levels correlated with a greater increase in antibodies post-boost, indicating antibody-mediated modulation of vaccine boosting.
  • Pre-existing antibodies in mice significantly inhibited antigen expression and B cell priming following mRNA vaccination.
  • The advantage of updated Omicron vaccines over original vaccines was contingent on the individual's pre-existing immunity (serostatus).

Conclusions:

  • Pre-existing immunity plays a crucial role in determining the host's response to mRNA vaccination.
  • These findings clarify conditions under which updated SARS-CoV-2 vaccines provide enhanced protection compared to original formulations.