PT - JOURNAL ARTICLE AU - Paulina Kaplonek AU - Deniz Cizmeci AU - Stephanie Fischinger AU - Ai-ris Collier AU - Todd Suscovich AU - Caitlyn Linde AU - Thomas Broge AU - Colin Mann AU - Fatima Amanat AU - Diana Dayal AU - Justin Rhee AU - Michael de St. Aubin AU - Eric J. Nilles AU - Elon R. Musk AU - Anil S. Menon AU - Erica Ollmann Saphire AU - Florian Krammer AU - Douglas A. Lauffenburger AU - Dan H. Barouch AU - Galit Alter TI - Subtle immunological differences in mRNA-1273 and BNT162b2 COVID-19 vaccine induced Fc-functional profiles AID - 10.1101/2021.08.31.458247 DP - 2021 Jan 01 TA - bioRxiv PG - 2021.08.31.458247 4099 - http://biorxiv.org/content/early/2021/08/31/2021.08.31.458247.short 4100 - http://biorxiv.org/content/early/2021/08/31/2021.08.31.458247.full AB - The successful development of several COVID-19 vaccines has substantially reduced morbidity and mortality in regions of the world where the vaccines have been deployed. However, in the wake of the emergence of viral variants, able to evade vaccine induced neutralizing antibodies, real world vaccine efficacy has begun to show differences across the mRNA platforms, suggesting that subtle variation in immune responses induced by the BNT162b2 and mRNA1273 vaccines may provide differential protection. Given our emerging appreciation for the importance of additional antibody functions, beyond neutralization, here we profiled the postboost binding and functional capacity of the humoral response induced by the BNT162b2 and mRNA-1273 in a cohort of hospital staff. Both vaccines induced robust humoral immune responses to WT SARS-CoV-2 and VOCs. However, differences emerged across epitopespecific responses, with higher RBD- and NTD-specific IgA, as well as functional antibodies (ADNP and ADNK) in mRNA-1273 vaccine recipients. Additionally, RBD-specific antibody depletion highlighted the different roles of non-RBD-specific antibody effector function induced across the mRNA vaccines, providing novel insights into potential differences in protective immunity generated across these vaccines in the setting of newly emerging VOCs.Competing Interest StatementG.A. is a founder and equity holder for Seromyx Systems Inc., an employee and equity holder for Leyden Labs, and has received financial support from Abbvie, BioNtech, GSK, Gilead, Merck, Moderna, Novartis, Pfizer, and Sanofi. D.D., J.R., A.S.M, and E.R.M. are employees of Space Exploration Technologies Corp. All other authors have declared that no conflict of interest exists.