The emerging coronavirus SARS-CoV-2 pandemic presents a global health emergency in urgent need of available treatments and vaccines. A group of Chinese researchers has isolated highly active human neutralizing antibodies, which may be the candidates for SARS-CoV-2 clinical interventions’ development.
On May 26, teams led by Dr. Zheng Zhang (Second Affiliated Hospital of Southern University of Science and Technology – Third People’s Hospital of Shenzhen), Dr. Linqi Zhang and Dr. Xinquan Wang from the Beijing Advanced Innovation Center for Structural Biology at Tsinghua University have made this ground-breaking finding. Their results were published in the high-impact academic journal, Nature (IF = 43.07), under the title, “Human neutralizing antibodies elicited by SARS-CoV-2 infection” as an “Accelerated Article Preview.” Their research has potentially laid the foundation for new antibodies to be used in the development of clinical interventions.
B lymphocytes are specialized cells that produce and secrete antibodies in the body and play a vital role in the fight against infections, tumors, and autoimmune diseases. Antibodies make up about 20% of plasma protein, patrolling the bloodstream for invading pathogens to implement its potent suppression and removal properties. Once a person is vaccinated against a pathogen, antibodies produced by these B cells play an essential role in protecting the body against the pathogens as part of its immune response.
SARS-CoV-2 entry into the target cells depends on binding between the receptor-binding domain (RBD) of the viral Spike protein and the ACE2 cell receptor. The research teams worked together to isolate and identify 206 monoclonal antibodies that specifically target RBD from single B lymphocytes. Monoclonal antibodies are made by identical immune cells that are all clones of a unique parent cell.
The single B lymphocytes in question were isolated from eight patients who had been infected with SARS-CoV-2. The research teams found the neutralizing activity for all the monoclonal antibodies in question is closely related to their ability to compete with ACE2 to bind with RBD.
Following this finding, the research teams focused on a series of highly active neutralizing monoclonal antibodies, focusing on antibodies such as P2B-2F6, P2C-1A3, and P2C-1F11.
Xinquan Wang’s team analyzed the crystal structure of the RBD-bound antibody P2B-2F6 showed the steric hindrance generated by antibody binding could deter the binding of viral RBD to ACE2. It means that the virus was unable to gain access to the cell.
These findings show that neutralizing antibodies, such as P2B-AF6, that target viral RBD and prevent the binding to ACE2 are excellent inhibitors and could be viral species-specific inhibitors. It means that the highly active neutralizing antibodies isolated and purified in this study could be potential candidates for the development of clinical interventions against COVID-19.
The foundation laid by this paper could lead to the development of therapeutic antibody drugs. The production and clinical application of highly active neutralizing antibodies are being promoted at present. The researchers aim to carry out animal tests as soon as possible before moving onto clinical trials to help society and curb the spread of COVID-19 and other human coronaviruses.
The co-first authors are Dr. Bin Ju (Second Affiliated Hospital of Southern University of Science and Technology – Third People’s Hospital of Shenzhen), Dr. Qi Zhang (School of Medicine, Tsinghua University), and Dr. Jiwan Ge (School of Life Sciences, Tsinghua University). The co-correspondent authors were Dr. Xinquan Wang (School of Life Sciences, Tsinghua University), Dr. Zheng Zhang (Second Affiliated Hospital of Southern University of Science and Technology – Third People’s Hospital of Shenzhen), and Dr. Linqi Zhang (School of Medicine, Tsinghua University).
This research was supported by the Shenzhen Science and Technology Innovation Committee, the National Protein Science Research (Beijing) Facilities, the Beijing Center for Advanced Innovation in Structural Biology, the Beijing Frontier Research Center for Biostructure, the Key Laboratory of Protein Science Ministry of Education and the National Key R&D Program.
Paper link: https://www.nature.com/articles/s41586-020-2380-z
