Alice Cho, Frauke Muecksch, Dennis Schaefer-Babajew, Zijun Wang, Shlomo Finkin, Christian Gaebler, Victor Ramos, Melissa Cipolla, Marianna Agudelo, Eva Bednarski, Justin DaSilva, Irina Shimeliovich, Juan Dizon, Mridushi Daga, Katrina Millard, Martina Turroja, Fabian Schmidt, Fengwen Zhang, Tarek Ben Tanfous, Mila Jankovic, Thiago Oliveira, Anna Gazumyan, Marina Caskey, Paul D Bieniasz, Theodora Hatziioannou, Michel C. Nussenzweig
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection produces B-cell responses that continue to evolve for at least one year. During that time, memory B cells express increasingly broad and potent antibodies that are resistant to mutations found in variants of concern. As a result, vaccination of coronavirus disease 2019 (COVID-19) convalescent individuals with currently available mRNA vaccines produces high levels of plasma neutralizing activity against all variants tested. Here, we examine memory B cell evolution 5 months after vaccination with either Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) mRNA vaccines in a cohort of SARS-CoV-2 naive individuals. Between prime and boost, memory B cells produce antibodies that evolve increased neutralizing activity, but there is no further increase in potency or breadth thereafter. Instead, memory B cells that emerge 5 months after vaccination of naive individuals express antibodies that are equivalent to those that dominate the initial response. We conclude that memory antibodies selected over time by natural infection have greater potency and breadth than antibodies elicited by vaccination. These results suggest that boosting vaccinated individuals with currently available mRNA vaccines would produce a quantitative increase in plasma neutralizing activity but not the qualitative advantage against variants obtained by vaccinating convalescent individuals.
Competing Interest Statement
The Rockefeller University has filed a provisional patent application in connection with this work on which M.C.N.is an inventor (US patent 63/021,387). The patent has been licensed by Rockefeller University to Bristol Meyers Squib.
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