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Merck

Pre-existing immunity modulates responses to mRNA boosters.

Cell reports (2023-03-02)
Tanushree Dangi, Sarah Sanchez, Min Han Lew, Bakare Awakoaiye, Lavanya Visvabharathy, Justin M Richner, Igor J Koralnik, Pablo Penaloza-MacMaster
RÉSUMÉ

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.

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Luciferase from Photinus pyralis (firefly), recombinant, expressed in E. coli, buffered aqueous solution, ≥10×1010 units/mg protein