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

Omicron (B.1.1.529) shows extensive escape from vaccine immunity, although vaccination reduces severe disease and death[1][1]. Boosting with vaccines incorporating variant spike sequences could possibly broaden immunity[2][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][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. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was supported by the Bill and Melinda Gates award INV-018944 (AS), National Institutes of Health award R01 AI138546 (AS), and South African Medical Research Council award 6084COAP2020 (AS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Blood samples used for plasma isolation and neutralization experiments and swabs for isolation of the ancestral/D614G and Delta viruses were obtained after written informed consent from adults with PCR-confirmed SARS-CoV-2 infection who were enrolled in a prospective cohort study at the Africa Health Research Institute approved by the Biomedical Research Ethics Committee at the University of KwaZulu-Natal (reference BREC/00001275/2020). The Beta virus was obtained from residual swab samples used for diagnostic testing by the National Health Laboratory Service (BREC approval reference BREC/00001510/2020). The Omicron/BA.1 virus was isolated from a residual swab sample with SARS-CoV-2 isolation from the sample approved by the University of the Witwatersrand Human Research Ethics Committee (HREC) (ref. M210752). The sample to isolate Omicron/BA.2 was collected after written informed consent as part of the COVID-19 transmission and natural history in KwaZulu-Natal, South Africa: Epidemiological Investigation to Guide Prevention and Clinical Care Centre for the AIDS Programme of Research in South Africa (CAPRISA) study and approved by the Biomedical Research Ethics Committee at the University of KwaZulu-Natal (reference BREC/00001195/2020, BREC/00003106/2021). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors. [1]: #ref-1 [2]: #ref-2 [3]: #ref-3