On January 12, the internationally renowned Journal of Virology published an online publication of the Zhou Paul research group of the Shanghai Institute of Pasteur of the Chinese Academy of Sciences entitled "Human monoclonal antibodies that recognize conserved epitopes of H5 hemagglutinin can broadly neutralize high The latest research results of "pathogenic avian influenza H5N1 virus". This is the first report that human neutralizing antibodies can broadly neutralize almost all types and subtypes of H5N1 viruses.
Determination of amino acid residues related to neutralizing epitope of monoclonal antibody 65C6
Since 1996, the highly pathogenic avian influenza H5N1 virus has infected more than 500 million poultry, and there have been increasing reports of human infection with the H5N1 virus in Asia, Africa and Europe. As of October 10, 2011, 566 cases of human infection have been diagnosed, including 332 deaths. Current vaccines often only protect similar virus strains.
In this study, Hu Hongxing, a PhD student at the Pasteur Institute in Shanghai, and others, under the guidance of Professor Zhou Paulo, used the highly sensitive H5N1 pseudovirus system to select memory B cells from patients who had recovered from the H5N1 virus but recovered 3 strains of human monoclonal antibodies against H5N1 virus. Among them, monoclonal antibody 65C6 can neutralize almost all types and subtypes of H5N1 virus except subtype 7.2, and has shown good prevention and protection in model organisms.
Through electron microscopic analysis of hemagglutinin and antibody complexes, combined with yeast display technology, the researchers found that monoclonal antibody 65C6 can recognize the conformational epitope located on the spherical head of hemagglutinin. This epitope is highly conserved on almost all hemagglutinin of H5N1, suggesting that this broad-spectrum neutralizing antibody can be used to treat patients infected with highly pathogenic avian influenza H5N1. In addition, based on the conserved epitope, an immunogen can be designed to induce a broad-spectrum neutralizing antibody response against the highly pathogenic avian influenza H5N1 against the epitope through immunization.
The project was completed in cooperation with Professor John Skehel of the British National Institute of Medicine and Professor Vincent Deubel of the Pasteur Institute in Cambodia, Professor Linqi Zhang of Tsinghua University and Professor Zhou Boping of the Third People's Hospital of Shenzhen.
The research was supported by the French Ministry of Health, the National Natural Science Foundation, the National Science and Technology Major Project, and the Li Ka Shing Foundation and the British Medical Research Foundation.
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