Broadly neutralizing antibody that protects Syrian hamsters in opposition to SARS-CoV-2 Omicron variants

Researchers on the AIDS Institute, The College of Hong Kong (HKU), Division of Microbiology, Faculty of Scientific Medication, the LKS School of Medication of The College of Hong Kong (HKUMed) and the State Key Laboratory of Rising Infectious Ailments, HKU, along with structural biologists at The Hong Kong College of Science and Know-how (HKUST), have demonstrated that ZCB11, a broadly neutralising antibody derived from an area mRNA-vaccinee in opposition to the spreading Omicron variants of SARS-CoV-2, shows potent antiviral actions in opposition to all variants of concern (VOCs), together with the dominantly spreading Omicron BA.1, BA1.1 and BA.2. Critically, both prophylactic or therapeutic ZCB11 administration protects lung an infection in opposition to Omicron viral problem in golden Syrian hamsters. The analysis paper is now printed on-line in Nature Communications.

Background

The strikingly excessive transmissibility and antibody evasion of SARS-CoV-2 Omicron variants have posed nice challenges to the efficacy of present vaccines and antibody immunotherapy. In response to the continual emergence of SARS-CoV-2 Omicron variants with unpredictable pathogenicity, common masking, quarantine and limitless viral testing need to be maintained, leading to social nervousness and financial disruption. It’s subsequently necessary to research into whether or not host immune response can generate broadly neutralising antibodies, which is crucial not just for antibody-based immunotherapy but additionally for vaccine optimisation to induce equally broad safety.

Analysis strategies and findings

On this examine, the HKUMed group has established an efficient platform of cloning know-how that natively pairs antibody genes from particular person human reminiscence B cells. Utilizing this system, the analysis group efficiently found ZCB11 after screening 34 BNT162b2-vaccinees in Hong Kong, and demonstrated that ZCB11 neutralises all VOCs together with Alpha (B.1.1.7), Beta (B.1.351), Gamma (P1), Delta (B.1.617.2) and Omicron (B.1.1.529) by testing each pseudoviruses and genuine stay viruses. Importantly, ZCB11 administration protects lung an infection in opposition to each stay Omicron and Delta viral challenges in golden Syrian hamsters respectively, underneath each prophylactic and therapeutic situations. Moreover, the HKUST collaborative group deciphered the advanced construction of ZCB11 and spike protein at atomic decision utilizing single particle cryo-EM, revealing the distinctive molecular mode of ZCB11 motion, which lays a stable basis for upcoming structure-guided antibody and vaccine optimisation.

Significance of the examine

‘The findings advised that ZCB11 is a promising antibody drug for biomedical interventions in opposition to pandemic SARS-CoV-2 variants of concern,’ remarked Professor Chen Zhiwei, Director of AIDS Institute and Professor of the Division of Microbiology, Faculty of Scientific Medication, HKUMed, who led the examine. ‘Though our findings implicate that the HKUMed group is on the world’s forefront of analysis and growth of human antibody medication and vaccines in opposition to COVID-19, we nonetheless urgently want to ascertain large-scale manufacturing capability and scientific translational hubs in Hong Kong, so as to meet its aspiration of changing into a world innovation centre.’

‘The high-resolution structural info enabled us to grasp the molecular mechanism of ZCB11 responding to a broad SARS-CoV-2 variant of concern,’ mentioned Professor Dang Shangyu, Assistant Professor of Division of Life Science, HKUST. ‘This examine depends on the state-of-the-art cryo-EM facility at HKUST, which demonstrated its functionality to help not solely analysis in structural biology, but additionally many different analysis fields, reminiscent of antibody growth on this examine.’

In regards to the analysis group

The analysis is led by Professor Chen Zhiwei, Director of AIDS Institute and Professor of the Division of Microbiology, Faculty of Scientific Medication, HKUMed; and was performed primarily by Mr Zhou Biao, PhD candidate. Dr Zhou Runhong, analysis officer; Dr Jasper Chan Fuk-woo, Scientific Affiliate Professor; Luo Mengxiao and Peng Qiaoli, PhD candidates; Dr Yuan Shuofeng, Assistant Professor on the Division of Microbiology, Faculty of Scientific Medication, HKUMed. Tang Bingjie and Liu Grasp, MPhil college students of Division of Life Science, HKUST, shared the primary authorship.

This collaborative group additionally contains Dr Bobo Mok Wing-yee, Scientific Officer; Chen Bohao; Dr Wang Pui, Scientific Officer; 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, Chairperson and Scientific Affiliate Professor; Professor Chen Honglin; Professor Yuen Kwok-yung, Henry Fok Professor in Infectious Ailments and Chair of Infectious Ailments, Division of Microbiology, Faculty of Scientific Medication, HKUMed and Director of the State Key Laboratory of Rising Infectious Ailments, The College of Hong Kong. Professor Dang Shangyu and Professor Chen Zhiwei shared the correspondence authorship.

Acknowledgements

This examine was supported by the Hong Kong Analysis Grants Council — Collaborative Analysis Fund (C7156‐20GF, C1134‐20GF and C5110‐20GF) and Well being and Medical Analysis Fund from the Meals and Well being Bureau (19181012); Shenzhen Science and Know-how Program (JSGG20200225151410198 and JCYJ20210324131610027); the Hong Kong Well being@InnoHK, Innovation and Know-how Fee, the Authorities of the Hong Kong Particular Administrative Area; and the China Nationwide Program on Key Analysis Undertaking (2020YFC0860600, 2020YFA0707500 and 2020YFA0707504); and donations from the Associates of Hope Schooling Fund in Hong Kong. Professor Chen Zhiwei’s group was additionally partly supported by the Hong Kong Analysis Grants Council — Theme‐based mostly Analysis Scheme (T11‐706/18‐N) and Wellcome Belief P86433.

All cryo-EM knowledge had been collected on the Organic Cryo-EM Heart at HKUST, generously supported by a donation from the Lo Kwee Seong Basis, along with help to Professor Dang Shangyu’s group from the Analysis Grants Council (RGC) of Hong Kong (ECS26101919, GRF16103321, C7009-20GF, C6001-21EF), Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou) (SMSEGL20SC01-L), Guangdong Fundamental and Utilized Fundamental Analysis Basis (2021A1515012460), Shenzhen Particular Fund for Native Science and Know-how Growth Guided by Central Authorities (2021Szvup140) and HKUST start-up and initiation grants.

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