BREAKTHROUGH! COVID-19 Antibodies: Chinese Researchers Identify Potent SARS-CoV-2 Neutralizing Antibodies
Source: COVID-19 Antibodies Jun 03, 2020 3 years, 10 months, 3 weeks, 1 day, 6 hours, 14 minutes ago
COVID-19 Antibodies: A collaborative research led by Peking University In Beijing has successfully identified multiple highly potent neutralizing antibodies against the SARS-CoV2 coronavirus, the causative virus of the respiratory/thrombotic disease COVID-19, from convalescent plasma by high-throughput single-cell sequencing.
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These neutralizing antibodies generated by the human immune system, can effectively prevent viruses from infecting cells. New results from animal studies showed that their neutralizing antibody provides a potential cure for COVID-19 as well as means for short-term prevention. This marks a major milestone in the fight against the pandemic.
The research findings has been published in the journal:
Cell.
https://www.cell.com/cell/pdf/S0092-8674(20)30620-6.pdf?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867420306206%3Fshowall%3Dtrue
The research was led by Dr Sunney Xie, Director of Beijing Advanced Innovation Center for Genomics (ICG) at Peking University (PKU) and was jointly conducted by Beijing Advanced Innovation Center for Genomics and Biomedical Pioneering Innovation Center of Peking University, Beijing YouAn Hospital of Capital Medical University, Institute of Laboratory Animal Science (ILAS) of Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, Beijing Institute of Microbiology and Epidemiology of Academy of Military Medical Sciences, Sino Biological, Inc., WuXi Biologics and Singlomics. The co-authors of this article are Dr Yunlong Cao, Dr Bin Su, Dr Xianghua Guo, Dr Wenjie Sun, Dr Yongqiang Deng, Dr Linlin Bao, Dr Qinyu Zhu. The corresponding authors are Dr Chuan Qin, Dr Chengfeng Qin, Dr Ronghua Jin, and Dr Sunney Xie.
Neutralization potency of BD-368-2 antibody against pseudovirus and authentic virus, IC50 reached 8pM and 100pM respectively. Credit: Beijing Advanced Innovation Center for Genomics, Biomedical Pioneering Innovation Center, Peking University
The research study which began on January 27, 2020 was supported by The People’s Government of Beijing Municipality, the Ministry of Science and Technology and the Ministry of Education of the People’s Republic of China.
The deadly pandemic has created an urgent need for highly effective drugs to cure COVID-19. However repurposed small-molecule drugs lack in specificity thus efficacy is compromised. Although plasma therapy has exhibited certain efficacy, it’s limited by convalescent plasma supply. The active component of plasma therapy is the target-specific neutralizing antibody. Antibody drugs as a kind of biologics have been successfully applied to treat viruses like AIDS, Ebola, and MERS. However, it is often time-consuming to develop neutraliz
ing antibodies suitable for clinical use, taking months or even years.
By utilizing their expertise in single-cell genomics, Dr Sunney Xie’s team at ICG, PKU in collaboration with researchers of Beijing YouAn Hospital collected blood samples from over 60 convalescent patients, among which 14 highly potent neutralizing antibodies were selected from 8,558 antigen-binding IgG1+ clonotypes.
Testing on the therapeutic and prophylactic efficacy of neutralizing antibodies on mice models (A) Therapeutic group (green), injected with BD-368-2 two hours after infection (n=3); prophylactic group (red), injected with BD-368-2 one day before infection (n=3); control group (blue) injected with nonrelevant antibody two hours after infection. (B) The rate of weight loss of therapeutic and prophylactic groups was significantly lower than that of the control group. (C) After 5 days, the viral load of therapeutic group decreased by ~ 2400 times; no viral load was detected in the prophylactic group. Credit: Beijing Advanced Innovation Center for Genomics, Biomedical Pioneering Innovation Center, Peking University
It was found that the most potent antibody, BD-368-2, exhibited an IC50 of 8pM and 100pM against pseudotyped and authentic SARS-CoV-2. Experiments on the authentic virus were completed in the P3 laboratory of the Academy of Military Medical Sciences.
Vivo studies have only just been completed using hACE2 transgenic mice model developed by Dr Chuan Qin’s lab at ILAS. The results showed that BD-368-2 antibody could provide strong therapeutic efficacy and prophylactic protection against SARS-CoV-2: When the BD-368-2 antibody was injected into infected mice, virus load was decreased by ~ 2400 times; when uninfected mice were injected with BD-368-2, they were protected from the virus infection.
The structural biologists Dr Xiaodong Su and Dr Junyu Xiao and their group members in the PKU team also obtained the 3.8Å Cryo-EM structure of a neutralizing antibody in complex with the Spike-ectodomain trimer. It revealed the antibody’s epitope overlaps with the ACE2 binding-site, which provides the structural basis of neutralization. Moreover, they showed that SARS-CoV-2 neutralizing antibodies could be selected with high efficiency based on similarities of their predicted structures to those of SARS-CoV neutralizing antibodies, hence greatly expediting the screening process.
(A&B) Cryo-EM structure of BD-23 Fab in complex with the Spike-ectodomain trimer (C) RBD/ACE2 complex structure overlays with RBD/ BD-23 Fab structure, which demonstrates BD-23 Fab can block S protein binding with ACE2. Credit: Beijing Advanced Innovation Center for Genomics, Biomedical Pioneering Innovation Center, Peking University
It was found that the potent neutralizing antibody could be used to develop drugs for both therapeutic intervention and prophylactic protection against SARS-CoV-2.
A few clinical trials are underway, and the research team has strong confidence in finding a cure.
Dr Sunney Xie commented, “If the COVID-19 epidemic reappears in the winter, our neutralizing antibody might be available by that time.”
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