Research Alert
Abstract Submission ID: 197
Newswise — mRNA vaccines have shown high efficacy in preventing severe COVID-19, but breakthrough infections, emerging variants, and waning antibody levels have warranted the use of boosters. Although mRNA boosters have been widely implemented, the extent to which pre-existing immunity influences the efficacy of boosters remains unclear. In a cohort of individuals primed with the mRNA-1273 or BNT 162b2 vaccines, we observed that lower spike-specific antibody levels before the boost were associated with higher fold-increase in spike-specific antibody levels after boost, suggesting that pre-existing antibodies to SARS-CoV-2 downmodulate the immunogenicity of mRNA-based vaccines. Similar effects were observed in mice that received mRNA-based SARS-CoV-2 vaccines AND HIV-1 vaccines. Our subsequent studies in mice show that pre-existing antibodies against the antigen encoded by the mRNA vaccine itself accelerate the clearance of vaccine antigen following booster vaccination, via Fc-dependent mechanisms, limiting the amount of antigen available to prime B cell responses. These data suggest that transient downmodulation of antibody effector functions may improve the efficacy of mRNA boosters against SARS-CoV-2 and other diseases.
RSS