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Abstract: Researchers from Shanghai University of Science and Technology Institute of Immunology, Scripps Research Institute in the United States, and Oxford University in the United Kingdom have screened multiple neutralizing antibodies against SARS-CoV-2 S protein in the natural combinatorial antibody library constructed more than 20 years ago.
Live viruses and mutants have super activity
.
Structural analysis revealed that unlike antibodies isolated from COVID-19 patients, these antibodies have obvious evolutionary characteristics such as somatic high frequency mutation (SHM) and novel binding methods
.
It reveals the possibility of long-term coexistence between the new coronavirus and humans
.
Keywords: Advanced Science, Combinatorial Antibody Library, Novel Coronavirus, Somatic Mutations Recently, Richard A.
Lerner/Yang Guang team, Institute of Immunochemistry, Shanghai University of Science and Technology, Richard A.
Lerner/Ian A.
Wilson, Scripps Research Institute, USA The team and the William James team of the University of Oxford in the United Kingdom have made important progress in the research on the novel coronavirus (SARS-CoV-2), and published the title "Neutralizing Antibodies to SARS-CoV-2 Selected from a Human Antibody Library Constructed Decades Ago" research paper
.
Researchers discovered that the natural and fully human combinatorial antibody library constructed 20 years ago contains neutralizing antibodies against SARS-CoV-2 S protein
.
These antibody molecules have obvious characteristics of immune evolution
.
These combined antibody molecules have super strong activity of inhibiting and neutralizing the COVID-19 virus, and have guiding significance for the development of therapeutic antibody drugs and effective virus vaccines
.
The new coronary pneumonia (COVID-19) caused by the persistent SARS-CoV-2 virus infection has become a global pandemic and has a fundamental impact on human health, life and social stability
.
A comprehensive understanding of the occurrence and development of the virus, as well as the development of effective treatment interventions, are critical to the current epidemic control
.
The Spike (S) protein exposed on the surface of the new coronavirus can bind to the human cell surface receptor angiotensin converting enzyme (ACE2), which is the main way for coronavirus to infect cells
.
Therefore, the S protein is the main target of the immune system response in the body, and it is also the focus of vaccine design and drug development.
More and more vaccines (mRNA vaccines) and therapeutic neutralizing antibody drugs are used to prevent and block SARS-CoV-2 virus.
Is being discovered one after another
.
Combinatorial antibody library technology is a method in which the diverse collection of antibodies of the individual B cell immune system and its antibody response history are reconstructed in a test tube through DNA rearrangement, combined and reproduced randomly
.
[1] Since the introduction of this technology in the 1980s, more than 70 monoclonal fully human antibodies have entered clinical studies, and 14 have been approved
.
Figure 1.
Screening system for neutralizing antibodies against spike protein receptor binding domains.
Yang Guang's group and Richard A.
Lerner's group, Shanghai University of Science and Technology Institute of Immunochemistry, aimed at SARS-CoV-2 S protein receptor binding domain (S- RBD), for the fully human natural combinatorial antibody library (collection of B cells with a diversity of >1011) constructed 20 years ago, multiple rounds of competitive screening were carried out using epitope targeting, and 3 high-definition S-RBD antibodies were obtained.
Specific, high-affinity monoclonal antibody
.
These antibody molecules have strong and effective neutralizing activity in pseudoviruses
.
The William James team at the University of Oxford confirmed that these antibodies also have a highly effective neutralizing activity in live viruses and their mutations
.
The team of Ian A.
Wilson of Scripps Research in the United States used X-ray crystal diffraction technology to analyze their molecular mechanism of action and found that S-B8 and S-E6 compete with ACE2 to bind to S-RBD.
The main binding effect, S-B8 is the antibody heavy chain, and S-E6 is the antibody light chain
.
Through the SHM analysis of the antibody, it was found that, unlike the targeted RBD neutralizing antibody with low SHM isolated in most patients with new coronary pneumonia, the antibody produced by the combined antibody library has a higher SHM, and some of the SHM residues are The key to SARS-CoV-2 RBD combination
.
What is interesting is that the heavy chain of the S-E6 antibody is IGHV4-31, which is less common in neutralizing antibodies isolated from patients with COVID-19 rehabilitation
.
His natural sequence does not bind strongly, but a 33NY34 sequence is generated through SHM in the CDR1 region of the heavy chain, which is consistent with the 32NY33 motif of IGHV3-53/3-66, which is more common in neocoronavirus neutralizing antibodies
.
This strong binding motif produced by SHM reveals that the antibodies in the combinatorial library may have undergone repeated stimulation of similar antigens in the human body, thereby evolving this strong binding sequence
.
The discovery of this phenomenon has important value for studying the interaction between viruses and their hosts and their co-evolution
.
Figure 2 Structural analysis of antigen-antibody complexes Qiang Min, assistant researcher of Yang Guang's research group, Institute of Immunochemistry, Shanghai University of Science and Technology, associate researcher Ma Peixiang, doctoral student Li Yu, and Liu Hejun, Ian A.
Wilson's research group of the Scripps Research Institute in the United States for the article The co-first authors, Richard A.
Lerner, Distinguished Professor of ShanghaiTech University, Distinguished Professor Yang Guang, and Ian A.
Wilson of the Scripps Research Institute in the United States are the co-corresponding authors of the article
.
WILEY paper information: Neutralizing Antibodies to SARS-CoV-2 Selected from a Human Antibody Library Constructed Decades AgoMin Qiang, Peixiang Ma, Yu Li, Hejun Liu, Adam Harding, Chenyu Min, Fulian Wang, Lili Liu, Meng Yuan, Qun Ji, Pingdong Tao, Xiaojie Shi, Zhean Li, Teng Li, Xian Wang, Yu Zhang, Nicholas C.
Wu, Chang-Chun D.
Lee, Xueyong Zhu, Javier Gilbert-Jaramillo, Chuyue Zhang, Abhishek Saxena, Xingxu Huang, Hou Wang, William James, Raymond A.
Dwek, Ian A.
Wilson*, Guang Yang*, Richard A.
Lerner* Advanced Science DOI: 10.
1002/advs.
202102181 Click "Read the original text" in the lower left corner to view the original text of the paper
.
Introduction to AdvancedScience Journal "Advanced Science" (Advanced Science) Wiley is a high-quality open source journal founded in 2014.
It publishes innovative achievements and cutting-edge progress in various fields such as materials science, physical chemistry, biomedicine, and engineering
.
The journal is dedicated to disseminating scientific research results to the public to the greatest extent, and all articles are freely available
.
The latest impact factor is 16.
806, and the 2020 SCI journals of the Chinese Academy of Sciences will be divided into the Q1 area of the material science category and the Q1 area of the engineering technology category
.
Press and hold the QR code on the official WeChat platform of AdvancedScienceNewsWiley's scientific research information.
Follow us to share cutting-edge information｜Focus on scientific research trends to publish scientific research news or apply for information sharing, please contact: ASNChina@Wiley.
com
Live viruses and mutants have super activity
.
Structural analysis revealed that unlike antibodies isolated from COVID-19 patients, these antibodies have obvious evolutionary characteristics such as somatic high frequency mutation (SHM) and novel binding methods
.
It reveals the possibility of long-term coexistence between the new coronavirus and humans
.
Keywords: Advanced Science, Combinatorial Antibody Library, Novel Coronavirus, Somatic Mutations Recently, Richard A.
Lerner/Yang Guang team, Institute of Immunochemistry, Shanghai University of Science and Technology, Richard A.
Lerner/Ian A.
Wilson, Scripps Research Institute, USA The team and the William James team of the University of Oxford in the United Kingdom have made important progress in the research on the novel coronavirus (SARS-CoV-2), and published the title "Neutralizing Antibodies to SARS-CoV-2 Selected from a Human Antibody Library Constructed Decades Ago" research paper
.
Researchers discovered that the natural and fully human combinatorial antibody library constructed 20 years ago contains neutralizing antibodies against SARS-CoV-2 S protein
.
These antibody molecules have obvious characteristics of immune evolution
.
These combined antibody molecules have super strong activity of inhibiting and neutralizing the COVID-19 virus, and have guiding significance for the development of therapeutic antibody drugs and effective virus vaccines
.
The new coronary pneumonia (COVID-19) caused by the persistent SARS-CoV-2 virus infection has become a global pandemic and has a fundamental impact on human health, life and social stability
.
A comprehensive understanding of the occurrence and development of the virus, as well as the development of effective treatment interventions, are critical to the current epidemic control
.
The Spike (S) protein exposed on the surface of the new coronavirus can bind to the human cell surface receptor angiotensin converting enzyme (ACE2), which is the main way for coronavirus to infect cells
.
Therefore, the S protein is the main target of the immune system response in the body, and it is also the focus of vaccine design and drug development.
More and more vaccines (mRNA vaccines) and therapeutic neutralizing antibody drugs are used to prevent and block SARS-CoV-2 virus.
Is being discovered one after another
.
Combinatorial antibody library technology is a method in which the diverse collection of antibodies of the individual B cell immune system and its antibody response history are reconstructed in a test tube through DNA rearrangement, combined and reproduced randomly
.
[1] Since the introduction of this technology in the 1980s, more than 70 monoclonal fully human antibodies have entered clinical studies, and 14 have been approved
.
Figure 1.
Screening system for neutralizing antibodies against spike protein receptor binding domains.
Yang Guang's group and Richard A.
Lerner's group, Shanghai University of Science and Technology Institute of Immunochemistry, aimed at SARS-CoV-2 S protein receptor binding domain (S- RBD), for the fully human natural combinatorial antibody library (collection of B cells with a diversity of >1011) constructed 20 years ago, multiple rounds of competitive screening were carried out using epitope targeting, and 3 high-definition S-RBD antibodies were obtained.
Specific, high-affinity monoclonal antibody
.
These antibody molecules have strong and effective neutralizing activity in pseudoviruses
.
The William James team at the University of Oxford confirmed that these antibodies also have a highly effective neutralizing activity in live viruses and their mutations
.
The team of Ian A.
Wilson of Scripps Research in the United States used X-ray crystal diffraction technology to analyze their molecular mechanism of action and found that S-B8 and S-E6 compete with ACE2 to bind to S-RBD.
The main binding effect, S-B8 is the antibody heavy chain, and S-E6 is the antibody light chain
.
Through the SHM analysis of the antibody, it was found that, unlike the targeted RBD neutralizing antibody with low SHM isolated in most patients with new coronary pneumonia, the antibody produced by the combined antibody library has a higher SHM, and some of the SHM residues are The key to SARS-CoV-2 RBD combination
.
What is interesting is that the heavy chain of the S-E6 antibody is IGHV4-31, which is less common in neutralizing antibodies isolated from patients with COVID-19 rehabilitation
.
His natural sequence does not bind strongly, but a 33NY34 sequence is generated through SHM in the CDR1 region of the heavy chain, which is consistent with the 32NY33 motif of IGHV3-53/3-66, which is more common in neocoronavirus neutralizing antibodies
.
This strong binding motif produced by SHM reveals that the antibodies in the combinatorial library may have undergone repeated stimulation of similar antigens in the human body, thereby evolving this strong binding sequence
.
The discovery of this phenomenon has important value for studying the interaction between viruses and their hosts and their co-evolution
.
Figure 2 Structural analysis of antigen-antibody complexes Qiang Min, assistant researcher of Yang Guang's research group, Institute of Immunochemistry, Shanghai University of Science and Technology, associate researcher Ma Peixiang, doctoral student Li Yu, and Liu Hejun, Ian A.
Wilson's research group of the Scripps Research Institute in the United States for the article The co-first authors, Richard A.
Lerner, Distinguished Professor of ShanghaiTech University, Distinguished Professor Yang Guang, and Ian A.
Wilson of the Scripps Research Institute in the United States are the co-corresponding authors of the article
.
WILEY paper information: Neutralizing Antibodies to SARS-CoV-2 Selected from a Human Antibody Library Constructed Decades AgoMin Qiang, Peixiang Ma, Yu Li, Hejun Liu, Adam Harding, Chenyu Min, Fulian Wang, Lili Liu, Meng Yuan, Qun Ji, Pingdong Tao, Xiaojie Shi, Zhean Li, Teng Li, Xian Wang, Yu Zhang, Nicholas C.
Wu, Chang-Chun D.
Lee, Xueyong Zhu, Javier Gilbert-Jaramillo, Chuyue Zhang, Abhishek Saxena, Xingxu Huang, Hou Wang, William James, Raymond A.
Dwek, Ian A.
Wilson*, Guang Yang*, Richard A.
Lerner* Advanced Science DOI: 10.
1002/advs.
202102181 Click "Read the original text" in the lower left corner to view the original text of the paper
.
Introduction to AdvancedScience Journal "Advanced Science" (Advanced Science) Wiley is a high-quality open source journal founded in 2014.
It publishes innovative achievements and cutting-edge progress in various fields such as materials science, physical chemistry, biomedicine, and engineering
.
The journal is dedicated to disseminating scientific research results to the public to the greatest extent, and all articles are freely available
.
The latest impact factor is 16.
806, and the 2020 SCI journals of the Chinese Academy of Sciences will be divided into the Q1 area of the material science category and the Q1 area of the engineering technology category
.
Press and hold the QR code on the official WeChat platform of AdvancedScienceNewsWiley's scientific research information.
Follow us to share cutting-edge information｜Focus on scientific research trends to publish scientific research news or apply for information sharing, please contact: ASNChina@Wiley.
com
