Today, nature, a leading academic journal, published an important research paper on new crown neutralizing antibodies online in the form of an “accelerated preview”. A team of researchers led by Chinese scientists has identified two highly specific new coronary neutralizing antibodies in the recoverers of the new coronary disease and confirmed the therapeutic and preventive potential of one of the neutralizing antibodies in the rhesus monkey model.
Yan Jinghua, Gao Fu, Wang Qihui, Institute of Microbiology, Chinese Academy of Sciences, Yuan Zhiming, Center for Biosecurity, Wuhan Institute of Virus Research, Chinese Academy of Sciences, and Wang Fusheng of the Center for Infectious Disease Treatment and Research at the Fifth Medical Center of the PLA General Hospital are the authors of the newsletter (Photo: Resources.
It is worth mentioning that this is also the first time since the outbreak of the new coronary virus, scientists in a non-human primate model to report anti-neo-coronavirus neutralizing experimental results, for guiding the design of human clinical trials, has important significance.
In this study, to find neutralizing antibodies that specifically identify new coronaviruses, the scientists extracted peripheral blood mononucleocytes from a recovering person with a new coronary disease and used the recombinant new coronavirus receptor binding domain (RBD) as “bait” to “fish” specific memory B cells from these mononucleic cells. By sequencing these B cells, the researchers found two monoclonal antibodies and named them CA1 and CB6 for follow-up studies.
Researchers found two monoclonal antibodies that specifically identify the new coronavirus RBD and prevent the new coronavirus from binding to ACE2 receptors (Photo: Supplied)
Cell experiments have shown that both monoclonal antibodies can prevent the RBD of the new coronavirus from binding to human ACE2 receptors on the cell surface. In other subsequent cell experiments, the two antibodies also showed good neutrality activity, while CB6 was more neutral.
The scientists went on to test the therapeutic and preventive effects of CB6 antibodies in animals. Specifically, the scientists used nine rhesus monkeys, divided them equally into three groups (treatment group, prevention group, control group) and infected them with a new coronavirus to observe the effects of neutralizing antibodies. Among them, the treatment group injected CB6 antibody on the first and third day after the infection, the prevention group injected CB6 antibody the day before the infection, and the control group injected a placebo of physiological saline (PBS).
In both the treatment group (blue) and the prevention group (red), cb6 can reduce the load of the new coronavirus. In addition, the antibody can also improve the pathological characteristics of animals (Image Source: Supplied)
The results of non-human primate experiments showed that on the 4th day of the new coronavirus infection, the virus titer in the body of the monkeys injected with CB6 antibodies significantly reduced, and a clear therapeutic effect was presented. In the prevention group, the injection of CB6 antibody also played a significant preventive effect, which had a significant protection for animals. The results of the pharynx showed that the animals in the prevention group had lower levels of the virus in their bodies.
Pathological analysis of the lungs of these monkeys also showed that CB6 reduced the associated lung damage associated with the new coronavirus. Based on these results, the researchers point out that the antibody not only inhibits the titration of the new coronavirus, but also improves the lung pathology associated with infection in the prevention and treatment groups.
In addition, the scientists also analyzed the crystal structure of neutralizing antibodies in order to understand their specific mechanisms of action. The analysis results show that CB6 antibodies identify the new coronavirus RBD, which binds to the human cell surface receptor ACE2, which can interfere with the interaction between the virus and the receptor. This also explains the mechanism of why this antibody shows the potential for treatment and prevention.
CB6 competes with ACE2 to interfere with the interaction between viruses and receptors (Photo: Resources 1)
The study was jointly conducted by the Institute of Microbiology of the Chinese Academy of Sciences, the Wuhan Virus Institute of the Chinese Academy of Sciences, the Beijing Ditan Hospital, the Fifth Medical Center of the PLA General Hospital, the Institute of Viral Diseases of the National Center for Disease Control and Prevention, and Junshi Bio.
Based on the potential of CB6, Reince B. Bio also partnered with Lilly to submit applications for clinical trials in China and the United States in the second quarter of this year and to launch human clinical studies.
Drug MingConde Content Team Mapping
Dr. Yan Jinghua, one of the leaders of the study and a researcher at the Institute of Microbiology of the Chinese Academy of Sciences, concluded in a press release that “this study presents two monoclonal antibodies with good neutralization activity, in which the antibody code-named CB6 shows stronger blocking capacity in in vitro experiments, not only more than 100 to 200 times higher than the affinity of the host cell receptor, but also highly overlapping with the binding region of the virus, making the virus and cell host much more likely.” At the same time, we have demonstrated the therapeutic and preventive capabilities of CB6 antibodies through non-human primate experiments, indicating that this candidate drug for the new coronavirus is promising and is very much expected to be further validated in clinical trials. “
Dr. Feng Hui, Chief Operating Officer of Junshi Bio, added, “Based on the company’s years of accumulation in the development of a full-life technology platform for antibody development, we have multi-pathed parallel development of candidate antibodies screened by microbes of the Chinese Academy of Sciences. As published in the journal Nature, one of the candidate antibodies showed strong neutrality against the new coronavirus. We look forward to working with Lilly Pharmaceuticals to advance the clinical application of this antibody in the second quarter. Junshi Bio will continue to increase research and development efforts, play its leading position in the field of innovative biological drugs, for China and the global anti-epidemic contribution. “