[PDF][PDF] Pre-existing immunity modulates responses to mRNA boosters

T Dangi, S Sanchez, MH Lew, B Awakoaiye… - Cell reports, 2023 - cell.com
T Dangi, S Sanchez, MH Lew, B Awakoaiye, L Visvabharathy, JM Richner, IJ Koralnik
Cell reports, 2023cell.com
Summary mRNA vaccines are effective in preventing severe COVID-19, but breakthrough
infections, emerging variants, and waning immunity warrant the use of boosters. Although
mRNA boosters are being 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 BNT162b2 vaccines, we report that lower antibody levels before boost are
associated with higher fold-increase in antibody levels after boost, suggesting that pre …
Summary
mRNA vaccines are effective in preventing severe COVID-19, but breakthrough infections, emerging variants, and waning immunity warrant the use of boosters. Although mRNA boosters are being 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 BNT162b2 vaccines, we report that lower antibody levels before boost are associated with higher fold-increase in antibody levels after boost, suggesting that pre-existing antibody modulates the immunogenicity of mRNA vaccines. Our studies in mice show that pre-existing antibodies accelerate the clearance of vaccine antigen via Fc-dependent mechanisms, limiting the amount of antigen available to prime B cell responses after mRNA boosters. These data demonstrate a "tug of war" between pre-existing antibody responses and de novo B cell responses following mRNA vaccination, and they suggest that transient downmodulation of antibody effector function may improve the efficacy of mRNA boosters.
cell.com