Antibody affinity maturation and cross-variant activity following SARS-CoV-2 mRNA vaccination: Impact of prior exposure and sex

Background: Limited knowledge exists regarding antibody affinity maturation following mRNA vaccination in naive vs. COVID-19 recovered individuals and potential sex differences. Methods: We elucidated post-vaccination antibody profiles of 69 naive and 17 COVID-19 convalescent adults using pseudovirus neutralization assay (PsVNA) covering SARS-CoV-2 WA-1, variants of concern (VOCs) and variants of interest (VOIs). Surface Plasmon Resonance (SPR) was used to measure antibody affinity against prefusion spike and receptor binding domain (RBD) and RBD mutants. Findings: Higher neutralizing antibodies were observed in convalescent vs. naive adults against, WA-1, VOCs, and VOIs. Antibody binding to RBD and RBD mutants showed lower binding of post-vaccination sera from naive compared with convalescent individuals. Moreover, we observed early antibody affinity maturation in convalescent individuals after one vaccine dose and higher antibody affinity after two doses compared with the naive group. Among the naive participants, antibody affinity against the SARS-CoV-2 prefusion spike was significantly higher for males than females even though there were no difference in neutralization titers between sexes. Interpretation: This study demonstrates the impact of prior infection on vaccine-induced antibody affinity maturation and difference in antibody affinity between males and females. Further studies are needed to determine whether antibody affinity may contribute to correlates of protection against SARS-CoV-2 and its variants. Published by Elsevier B.V.

Automated summary

This study highlights the differences in antibody affinity maturation between individuals with prior COVID-19 infection and naive individuals post mRNA vaccination. Higher neutralizing antibodies were observed in convalescent individuals compared to naive individuals, along with differences in antibody binding and affinity. Additionally, males showed significantly higher antibody affinity against SARS-CoV-2 prefusion spike compared to females among the naive participants. Further research is needed to determine the role of antibody affinity in protection against SARS-CoV-2 and its variants.