Study suggests ZCB11 is promising antibody against all concerning SARS-CoV-2 variants


Researchers from the AIDS Institute, University of Hong Kong (HKU), Department of Microbiology, School of Clinical Medicine, LKS Faculty of Medicine, University of Hong Kong (HKUMed) and from the State Key Laboratory of Emerging Infectious Diseases, HKU, in collaboration with structural biologists from the Hong Kong University of Science and Technology (HKUST), demonstrated that ZCB11, a broadly neutralizing antibody derived from a local mRNA vaccine against the spreading Omicron variants of SARS-CoV-2, displays potent antiviral activities against all variants of concern (COVs), including the dominant spreading Omicron BA.1, BA1.1 and BA.2. Critically, prophylactic or therapeutic administration of ZCB11 protects lung infection against Omicron virus challenge in golden Syrian hamsters. The research paper is now published online at Nature Communication.

Background

The surprisingly high transmissibility and antibody evasion of SARS-CoV-2 Omicron variants have posed great challenges to the effectiveness of current vaccines and antibody immunotherapy. In response to the continued emergence of SARS-CoV-2 Omicron variants with unpredictable pathogenicity, universal masking, quarantine, and endless viral testing must be maintained, resulting in social anxiety and economic disruption. It is therefore important to determine whether the host immune response can generate broadly neutralizing antibodies, which is essential not only for antibody-based immunotherapy, but also for vaccine optimization to induce a equally broad protection.

Research methods and results

In this study, the HKUMed team implemented an efficient cloning technology platform that natively matches the antibody genes of individual human memory B cells. Using this technique, the research team successfully discovered ZCB11 after screening 34 BNT162b2 vaccinees in Hong Kong, and demonstrated that ZCB11 neutralizes all VOCs, including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P1), Delta (B.1.617.2) and Omicron (B.1.1.529) by testing both pseudovirus and authentic live virus. Importantly, administration of ZCB11 protected lung infection against Omicron and Delta live virus challenge in golden Syrian hamsters, respectively, under prophylactic and therapeutic conditions. Furthermore, the HKUST collaborative team deciphered the complex structure of ZCB11 and the spike protein at atomic resolution using a single cryo-EM particle, revealing the unique molecular mode of action of ZCB11, which lays a solid foundation for future structure-guided antibody and vaccine optimization.

Significance of the study

“The results suggest that ZCB11 is a promising antibody drug for biomedical interventions against concerning variants of pandemic SARS-CoV-2,” remarked Professor Chen Zhiwei, Director of the AIDS Institute and Professor of the Department of Microbiology. , School of Clinical Medicine, HKUMed, who led the study. “While our findings imply that the HKUMed team is at the global forefront of researching and developing human antibody-based drugs and vaccines against COVID-19, we still urgently need to establish manufacturing capacity. scale and clinical translation centers in Hong Kong, in order to fulfill its aspiration to become an international center of innovation.

The high-resolution structural information allowed us to understand the molecular mechanism of ZCB11 responding to a concerning broad variant of SARS-CoV-2. This study builds on HKUST’s state-of-the-art cryo-EM facility, which has demonstrated its ability to support not only structural biology research, but also many other areas of research, such as antibody development in this study.

Professor Dang Shangyu, Assistant Professor of Life Sciences Division, HKUST

About the research team

The research is led by Professor Chen Zhiwei, Director of the AIDS Institute and Professor of the Department of Microbiology, School of Clinical Medicine, HKUMed; and was conducted mainly by Mr. Zhou Biao, PhD student. Dr. Zhou Runhong, Research Officer; Dr. Jasper Chan Fuk-woo, Associate Clinical Professor; Luo Mengxiao and Peng Qiaoli, doctoral students; Dr. Yuan Shuofeng, Assistant Professor in the Department of Microbiology, School of Clinical Medicine, HKUMed. Tang Bingjie and Liu Hang, master’s students from the Division of Life Sciences, HKUST, shared the first authorship.

This collaborative team also includes Dr. Bobo Mok Wing-yee, Scientific Officer; Chen Bohao; Dr. Wang Pui, Chief Scientist; Vincent Poon Kwok-man; Dr. Chu Hin, assistant professor; Chris Chan Chung-sing, Jessica Tsang Oi-ling, Chris Chan Chun-yiu, Au Ka-kit, Man Hiu-on, Lu Lu, Dr. Kelvin To Kai-wang, President and Associate Clinical Professor; Professor Chen Honglin; Professor Yuen Kwok-yung, Henry Fok Professor of Infectious Diseases and Chairman of Infectious Diseases, Department of Microbiology, School of Clinical Medicine, HKUMed and Director of State Key Laboratory of Emerging Infectious Diseases, University of Hong Kong. Professor Dang Shangyu and Professor Chen Zhiwei shared authorship of the correspondence.

Source:

The University of Hong Kong

Journal reference:

Zhou, B. et al. (2022) Broadly neutralizing antibody protects Syrian hamsters against SARS-CoV-2 Omicron challenge. Communication Nature. doi.org/10.1038/s41467-022-31259-7.

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