Chinese scientists have successfully developed a broad-spectrum humanized genetically engineered monoclonal antibody against novel coronavirus

August 19, according to the official Wechat official account of the Institute of Microbiology of the Chinese Academy of Sciences, the Yan Jinghua team of the Institute of Microbiology of the Chinese Academy of Sciences joined the Wang Chenhui team of Huazhong University of Science and Technology, the Xiao Junyu team of Peking University, the Wang Youchun team of the China Institute for Food and Drug Control, the Tan Wenjie team of the Chinese Center for Disease Control and Prevention, and Shanghai Junshi Biopharmaceutical Technology Co., Ltd. The research paper was published online on Nature Communications. In this paper, a blocking antibody targeting multiple coronavirus invading receptor ACE2 was reported for the first time. This antibody can effectively prevent and treat novel coronavirus (SARS-CoV-2) and its mutants from infecting host cells and model animals, and show good safety in non-human primates.

Firstly, through rapid screening and humanized modification of antibodies, a blocking monoclonal antibody h11B11 targeting human ACE2 receptor was obtained. through the neutralization evaluation of pseudoviruses and real viruses of various coronaviruses, it was confirmed that the antibody h11B11 had good inhibitory activity against SARS-CoV, SARS-CoV-2 and their mutants. This antibody combined with novel coronavirus therapeutic antibody CB6 developed in the early stage of Microbiology Research Institute can synergistically improve the neutralizing activity.

The full text of Institute of Microbiology, Chinese Academy of Sciences is as follows:

Chinese scientists have successfully developed a broad-spectrum humanized genetically engineered monoclonal antibody against COVID-19 virus.

Yan Jinghua team of Institute of Microbiology, Chinese Academy of Sciences, together with team Wang Chenhui of Huazhong University of Science and Technology, team Xiao Junyu of Peking University, team Wang Youchun of China Research Institute for Food and Drug Control, team Tan Wenjie of Chinese Center for Disease Control and Prevention, Shanghai Junshi Biopharmaceutical Technology Co., Ltd., published their research paper online on Nature Communications ("A broadly neutralizing humanized ACE2-targeting antibody againstSARS-CoV-2 variants").

This paper reports for the first time a blocking antibody targeting multiple coronavirus invasion receptors ACE2, which can effectively prevent and treat the infection of host cells and model animals by novel coronavirus (SARS-CoV-2) and his mutants, and show good safety in non-human primates.

Firstly, through rapid screening and humanized modification of antibodies, a blocking monoclonal antibody h11B11 targeting human ACE2 receptor was obtained. through the neutralization evaluation of pseudoviruses and real viruses of various coronaviruses, it was confirmed that the antibody h11B11 had good inhibitory activity against SARS-CoV, SARS-CoV-2 and their mutants. This antibody combined with novel coronavirus therapeutic antibody CB6 developed in the early stage of Microbiology Research Institute can synergistically improve the neutralizing activity.

CB6 McAb is an antibody targeting COVID-19 virus S protein RBD, jointly developed by Academician Gao Fu of Microbiology Research Institute and Yan Jinghua team, and has been authorized for emergency use in the United States, European Union, India and other countries.

Figure 1. H11B11 monoclonal antibody can neutralize SARS-CoV,SARS-CoV-2 and its mutant virus

The researchers further evaluated the activity of the antibody in vivo by infecting hACE2 transgenic mice with SARS-CoV-2. The results showed that compared with the placebo group, no virus was detected in the lungs of mice in the prophylaxis group; the virus titer in the lungs of mice in the treatment group was significantly lower; and the results of lung pathological sections also showed that the pathological changes of the lungs of the mice in the preventive and therapeutic groups were significantly improved (figure 2).

Picture 2.h11B11 Monoclonal Antibody for Prevention and treatment of novel coronavirus infection in mice

Because ACE2 receptor can maintain blood pressure balance, antibody h11B11 binding to ACE2 receptor may affect its physiological function.

The researchers used the cynomolgus monkey model to evaluate the preclinical safety of h11B11 antibody. Four male cynomolgus monkeys were randomly divided into two groups. After repeated intravenous infusion (once a week for three weeks; high dose group: 180 mg/kg, low dose group: 60 mg/kg), blood pressure and clinicopathological changes (hematology and serum biochemistry) were monitored.

The results showed that the blood pressure and blood chemical toxicological indexes of crab-eating monkeys did not change significantly even after three times of high-dose administration of h11B11 antibody, which proved that the antibody had good safety in vivo (Fig. 3).

Figure 3.h11B11 monoclonal antibody has good safety in crab-eating monkeys.

In order to clarify the mechanism of action and binding epitopes of h11B11 antibody, the researchers further analyzed the crystal structure of h11B11 and ACE2, which showed that the antibody mainly binds to the α-helix domain of the N-terminal of ACE2 receptor; the antibody blocks the binding of SARS-CoV and SARS-CoV-2 RBD regions to ACE2 receptors through epitope competition and steric hindrance effect to inhibit virus invasion into host cells (figure 4).

Figure 4. Analysis of the blocking mechanism of h11B11 antibody

Dr. du Yanyun, School of Life, Huazhong University of Science and Technology, Shi Rui, postdoctoral fellow, Institute of Microbiology, Chinese Academy of Sciences, and Dr. Zhang Ying, Peking University, are the co-first authors. Tan Wenjie, researcher of Chinese Center for Disease Control and Prevention, Wang Youchun, researcher of China Institute of Food and Drug Control, Professor Wang Chenhui, School of Life, Huazhong University of Science and Technology and Yan Jinghua Research Institute, Institute of Microbiology, Chinese Academy of Sciences.