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Priming conditions shape breadth of neutralizing antibody responses to sarbecoviruses

Vaccines that are broadly cross-protective against current and future SARS-CoV-2 variants of concern (VoC) or across the sarbecoviruses subgenus remain a priority for public health. Virus neutralization is the best available correlate of protection. To define the magnitude and breadth of cross-neutr...

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Published in:Nature communications 2022-10, Vol.13 (1), p.6285-12, Article 6285
Main Authors: Jia, Janice Zhirong, Tan, Chee Wah, Cheng, Samuel M. S., Gu, Haogao, Yeoh, Aileen Ying Yan, Mok, Chris Ka Pun, Wang, Yanqun, Zhao, Jincun, Leung, Nancy H. L., Cowling, Benjamin J., Poon, Leo L. M., Hui, David S. C., Wang, Linfa, Peiris, Malik, Valkenburg, Sophie A.
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Language:English
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Summary:Vaccines that are broadly cross-protective against current and future SARS-CoV-2 variants of concern (VoC) or across the sarbecoviruses subgenus remain a priority for public health. Virus neutralization is the best available correlate of protection. To define the magnitude and breadth of cross-neutralization in individuals with different exposure to SARS-CoV-2 infection and vaccination, we here use a multiplex surrogate neutralization assay based on virus spike receptor binding domains of multiple SARS-CoV-2 VoC, as well as related bat and pangolin viruses. We include sera from cohorts of individuals vaccinated with two or three doses of mRNA (BNT162b2) or inactivated SARS-CoV-2 (Coronavac or Sinopharm) vaccines with or without a history of previous SARS-CoV-2 or SARS-CoV-1 infection. SARS-CoV-2 or SARS-CoV-1 infection followed by BNT162b2 vaccine, Omicron BA.2 breakthrough infection following BNT162b2 vaccine or a third dose of BNT162b2 following two doses of BNT162b2 or Coronavac elicit the highest and broadest neutralization across VoCs. For both breadth and magnitude of neutralization across all sarbecoviruses, those infected with SARS-CoV-1 immunized with BNT162b2 outperform all other combinations of infection and/or vaccination. These data may inform vaccine design strategies for generating broadly neutralizing antibodies to SARS-CoV-2 variants or across the sarbecovirus subgenus. Vaccination and infection history determine the breadth of neutralizing antibody response to SARS-CoV-2 variants and other sarbecoviruses with breakthrough or natural infection combined with vaccination or booster vaccination with mRNA vaccine providing highest neutralization.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-022-34038-6