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Modeling Antibody Kinetics Post-mRNA Booster Vaccination and Protection Durations Against SARS-CoV-2 Infection.

Luis J Ponce1, Yuqian Wang1, Ananya Singh1

  • 1Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.

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|August 6, 2025
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Summary

Booster vaccines offer protection against SARS-CoV-2 infection, but antibody levels wane over time. Higher antibody levels after boosting correlate with reduced infection risk, informing optimal booster timing.

Keywords:
COVID‐19 breakthrough infectionsCOVID‐19 vaccinesSARS‐CoV‐2immunoglobulin Aimmunoglobulin Gsurvival analysis

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Area of Science:

  • Immunology
  • Infectious Diseases
  • Vaccinology

Background:

  • Understanding SARS-CoV-2 antibody dynamics post-booster vaccination is crucial for determining protection duration.
  • Booster immunizations aim to restore and enhance immunity against evolving viral variants.

Purpose of the Study:

  • To map the kinetics of SARS-CoV-2 specific IgA and IgG antibodies after booster vaccination.
  • To analyze the association between antibody levels and the risk of breakthrough infection.
  • To predict the duration of protection against SARS-CoV-2 infection post-booster.

Main Methods:

  • Longitudinal antibody data collection at baseline, 28, 180, and 360 days post-booster.
  • Nonlinear mixed effects modeling to analyze antibody kinetics against wild-type and Omicron BA.1 spike proteins.
  • Survival analysis to assess the correlation between antibody levels and infection risk.

Main Results:

  • Antibody levels waned faster after Pfizer-BioNTech BNT162b2 booster than Moderna mRNA-1273.
  • Higher antibody levels (WT IgG, BA.1 IgA) at day 28 post-booster were linked to reduced infection risk.
  • A BA.1 IgA response of 20% is needed for 80% protection over 155 days at medium COVID-19 incidence.

Conclusions:

  • Booster vaccine choice impacts antibody kinetics and waning rates.
  • Antibody levels are a significant predictor of protection duration against SARS-CoV-2 infection.
  • Findings can inform optimal SARS-CoV-2 booster vaccination strategies and timing.