Abstract

The induction of broadly neutralizing antibodies (bnAbs) against viruses requires the specific activation of human B cell receptors (BCRs) by viral epitopes. Following BCR activation, B cells can undergo germinal center–dependent and –independent pathways to generate both long-term and short-term epitope-specific memory responses. However, the regulation of B cell fate after BCR activation remains incompletely understood. Here, the speaker will report that a human isoform of PD-1, namely Δ42PD-1, plays a critical role in regulating B cell fate following BCR activation. While HIV-1 promotes B cell apoptosis via the epitope–BCR–Δ42PD-1 axis during chronic infection, SARS-CoV-2 does not appear to activate this pathway after breakthrough infections. This allows for more robust induction of bnAbs by engaging multiple highly conserved conformational “Jing” epitopes, as revealed by CryoEM analysis.

“Jing” follows the Chinese philosophy: “unchanging principles are the best response to change”. Consequently, bnAbs are induced not only against a broad range of evolving SARS-CoV-2 variants but also against pan-sarbecoviruses, including SARS-CoV-1 and SARS-CoV-2 variants, as well as related pangolin-CoV and bat-CoV strains. These findings have important implications for understanding human B cell immunity and for the design of novel vaccines against pan-sarbecoviruses.

About the Speaker

Prof. CHEN Zhiwei received his PhD from the New York University School of Medicine in 1996 and, by 2002, had progressed from an NIH F32 Postdoctoral Fellow to Assistant Professor at the Aaron Diamond AIDS Research Center of The Rockefeller University. In 2007, he joined the Li Ka Shing Faculty of Medicine of the University of Hong Kong (HKU) as an Associate Professor and Founding Director of the AIDS Institute. He is a former Chairman of the Hong Kong Society for Immunology and an Executive Committee Member of the China AIDS Vaccine Initiative. He also served as a Member of the Hong Kong Advisory Council on AIDS for the HKSAR Department of Health from 2008 to 2014. He is currently a Chair Professor of Immunology and Immunotherapy in the Department of Microbiology at HKU. He was conferred the Suen Chi-Sun Professorship in Clinical Science in 2024.

Prof. Chen’s research focuses on AIDS, SARS and COVID-19 pathogenesis and immunotherapy, with an emphasis on the early events of viral infection. He pioneered the creation of HKU-patented platforms of technologies, including the PD1-based vaccine, the tandem anti-HIV-1 bi-specific antibody, and an anti-Δ42PD1 antibody drug for viral infection and cancer. Clarivate Analytics has ranked him among the top 1% of researchers worldwide by citations and a Highly Cited Researcher in 2022, 2023 and 2024. He has won numerous research grants as PI from, for example, NIH RO1, amfAR and the Gates Foundation among others. He also won the HKU Knowledge Exchange Excellence Award (2019), Outstanding Researcher Award (2021), Outstanding Research Student Supervisor Award (2021) and Faculty Outstanding Research Output Award (2023).

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