Anti-SARS-CoV-2 receptor-binding domain antibody evolution after mRNA vaccination

TLDR

SARS‑CoV‑2 infection elicits B‑cell responses that continue to evolve for at least a year, and vaccination of convalescent individuals with mRNA vaccines induces high levels of plasma neutralizing activity against all tested variants. The study aims to examine memory B‑cell evolution five months after mRNA vaccination in SARS‑CoV‑2‑naïve individuals. The authors assessed memory B‑cell responses five months post‑vaccination with either mRNA‑1273 or BNT162b2 in a cohort of naïve participants. Memory B cells after prime‑boost show increased neutralizing activity, but five months later the antibody repertoire reverts to the initial response, with vaccination‑elicited plasma neutralizing potency higher than that from natural infection, yet boosting may raise plasma activity without matching the breadth achieved by vaccinating convalescent individuals.

Abstract

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 concern 1 . 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 1,2 . 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.