Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection produces B cell responses that continue to evolve for at least a year. During that time, memory B cells express increasingly broad and potent antibodies that are resistant to mutations found in variants of concern1. 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 tested1,2. Here we examine memory B cell evolution five months after vaccination with either Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) mRNA vaccine 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 five months after vaccination of naive individuals express antibodies that are similar to those that dominate the initial response. While individual memory antibodies selected over time by natural infection have greater potency and breadth than antibodies elicited by vaccination, the overall neutralizing potency of plasma is greater following vaccination. These results suggest that boosting vaccinated individuals with currently available mRNA vaccines will increase plasma neutralizing activity but may not produce antibodies with equivalent breadth to those obtained by vaccinating convalescent individuals.
Highlights
This is a PDF file of a peer-reviewed paper that has been accepted for publication
P B cells express increasingly broad and potent antibodies that are resistant to mutations found in variants of concern[1]
The increase in neutralizing activity between the first and memory cells increased after the boost, IgM-expressing memory B cells second vaccine dose was associated with a decrease in the percentthat made up 23% of the memory compartment after the prime were age of non-neutralizing antibodies and increased representation of neutralizing antibodies (p= 0.003, the same mutant pseudotype viruses (Fig. 4c, Supplementary Table 8)
Summary
Alice Cho[1,4], Frauke Muecksch[2,4], Dennis Schaefer-Babajew[1,4], Zijun Wang[1,4], Shlomo Finkin[1,4], Christian Gaebler[1], Victor Ramos[1], Melissa Cipolla[1], Pilar Mendoza[1], Marianna Agudelo[1], Eva Bednarski[2], Justin DaSilva[2], Irina Shimeliovich[1], Juan Dizon[1], Mridushi Daga[1], Katrina Millard[1], Martina Turroja[1], Fabian Schmidt[2], Fengwen Zhang[2], Tarek Ben Tanfous[1], Mila Jankovic[1], Thiago Y. The geometric mean ELISA half-maximal concentration (EC50) of the antibodies obtained after prime, and 1.3- and 5-months after the second dose was 3.5, 2.9 and 2.7 ng/ml respectively, suggesting no major change in binding over time after vaccination (Extended Data Fig. 6, Supplementary Table 5–6). E selected antibodies with comparable neutralizing activity obtained from the 1.3- and 5-month time points The increase in potency and breadth in the memory compartment that develops after natural infection accounts for the exceptional responses to Wuhan Hu-1 and its variants that convalescent individuals develop when boosted with mRNA vaccines[1,5]. Whether an additional by persisting clones obtained 1.3 and 5 months after vaccination against boost with Wuhan-Hu-based or variant vaccines or re-infection will elicit development of memory B cells expressing antibodies showing 23.
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