Omicron BA.1 breakthrough infection drives cross-variant neutralization and memory B cell formation against conserved epitopes

Omicron is the evolutionarily most distinct severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant of concern (VOC) to date. We report that Omicron BA.1 breakthrough infection in BNT162b2-vaccinated individuals resulted in strong neutralizing activity against Omicron BA.1, BA.2, and previous SARS-CoV-2 VOCs but not against the Omicron sublineages BA.4 and BA.5. BA.1 breakthrough infection induced a robust recall response, primarily expanding memory B (BMEM) cells against epitopes shared broadly among variants, rather than inducing BA.1-specific B cells. The vaccination-imprinted BMEM cell pool had sufficient plasticity to be remodeled by heterologous SARS-CoV-2 spike glycoprotein exposure. Whereas selective amplification of BMEM cells recognizing shared epitopes allows for effective neutralization of most variants that evade previously established immunity, susceptibility to escape by variants that acquire alterations at hitherto conserved sites may be heightened.

Automated summary

The Omicron BA.1 breakthrough infection in BNT162b2-vaccinated individuals showed strong neutralizing activity against Omicron BA.1, BA.2, and previous SARS-CoV-2 variants. The memory B cells induced by the breakthrough infection targeted epitopes shared broadly among variants. The vaccination-imprinted memory B cell pool was capable of remodeling in response to heterologous SARS-CoV-2 spike glycoprotein exposure. However, variants that acquire alterations at conserved sites may have increased susceptibility to immune escape.