Priming conditions shape breadth of neutralizing antibody responses to sarbecoviruses

Janice Zhirong Jia, Chee Wah Tan, Samuel M. S. Cheng, Haogao Gu, Aileen Ying Yan Yeoh, Chris Ka Pun Mok, Yanqun Wang, Jincun Zhao, Nancy H. L. Leung, Benjamin J. Cowling, Leo L. M. Poon, David S. C. Hui, Linfa Wang, Malik Peiris and Sophie A. Valkenburg ()
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Janice Zhirong Jia: The University of Hong Kong
Chee Wah Tan: National University of Singapore
Samuel M. S. Cheng: The University of Hong Kong
Haogao Gu: The University of Hong Kong
Aileen Ying Yan Yeoh: National University of Singapore
Chris Ka Pun Mok: The Chinese University of Hong Kong
Yanqun Wang: First Affiliated Hospital of Guangzhou Medical University
Jincun Zhao: First Affiliated Hospital of Guangzhou Medical University
Nancy H. L. Leung: The University of Hong Kong
Benjamin J. Cowling: The University of Hong Kong
Leo L. M. Poon: The University of Hong Kong
David S. C. Hui: The Chinese University of Hong Kong
Linfa Wang: National University of Singapore
Malik Peiris: The University of Hong Kong
Sophie A. Valkenburg: The University of Hong Kong

Nature Communications, 2022, vol. 13, issue 1, 1-12

Abstract: Abstract 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.

Date: 2022
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DOI: 10.1038/s41467-022-34038-6

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