Beta infection combined with Pfizer BNT162b2 vaccination leads to broadened neutralizing immunity against Omicron

Abstract Omicron (B.1.1.529) shows extensive escape from vaccine immunity, although vaccination reduces severe disease and death 1 . Boosting with vaccines incorporating variant spike sequences could possibly broaden immunity 2 . One approach to choose the variant may be to measure immunity elicited by vaccination combined with variant infection. Here we investigated Omicron neutralization in people infected with the Beta (B.1.351) variant and subsequently vaccinated with Pfizer BNT162b2. We observed that Beta infection alone elicited poor Omicron cross-neutralization, similar to what we previously found 3 with BNT162b2 vaccination alone or in combination with ancestral or Delta virus infection. In contrast, Beta infection combined with BNT162b2 vaccination elicited neutralization with substantially lower Omicron escape.