The research team of Professor Gao Feng and Professor Yu Xianghui from the School of Life Sciences of Jilin University took the rhesus monkey animal model with the longest reported infection time as the research object, and analyzed its broad-spectrum neutralizing activity induced in vivo
J038 broad-spectrum neutralizing antibody repertoire against specific epitopes was obtained by antibody isolation
This work studies antibody lineages and the mutation of viral envelope proteins in vivo, traces the evolution of broadly neutralizing antibodies and co-evolution with SHIV , and analyzes the similarities of broadly neutralizing antibodies produced in non-human primates and humans It provides theoretical and experimental basis for better application of rhesus monkey model to evaluate HIV-1
The developmental details and identification features of this J038 lineage antibody provide new insights into the future research and application of V2 -targeting broad-spectrum neutralizing antibodies
The research results were published online in the academic journal Advanced Science on March 24 , 2022 ( Development of Neutralization Breadth against Diverse HIV-1 by Increasing Ab–Ag Interface on V2 ) .
The first completion unit of the thesis is the School of Life Sciences, Jilin University.
The first author is Gao Nan, a doctoral student from the School of Life Sciences, Professor Xianghui Yu and Professor Gao Feng of Jilin University, Professor Tongqing Zhou of the National Institutes of Health Vaccine Research Center, and the Chinese Academy of Medical Sciences.
Qin Chuan from the Institute of Laboratory Animal Research is the co-corresponding author of the paper .
With the maturity of antibody isolation technology and the in-depth understanding of the mechanism of antibody - antigen evolution, a large number of broad-spectrum neutralizing antibodies against HIV-1
have been isolated and studied in depth .
Due to the homology of genetic backgrounds, non-human primate models are widely used in the field of AIDS research
However, little is known about whether broadly neutralizing antibodies similar to those of human origin can be produced in non-human primates and whether they have evolved and matured in a similar manner to antibodies in humans
In this regard, Professor Gao Feng and Professor Yu Xianghui's team have long-term followed and studied Chinese-origin rhesus monkeys infected with human / simian immunodeficiency chimeric virus ( SHIV ) carrying HIV-1 envelope protein gene for 7 years, and in their bodies The production of HIV-1 broad- spectrum neutralizing activity with epitopes similar to human-derived broad-neutralizing antibodies was detected .
Subsequently, the team isolated the J038 lineage of broad-spectrum neutralizing antibodies against the V2 region of the HIV-1 envelope protein in the rhesus monkey G1015R (where the J038 broad-spectrum reached ~54% ), which is also currently reported to be isolated from SHIV infection.
The highest broad-spectrum antibody in monkeys (Figure 1 ) .
And through the cooperation with Professor Zhou Tongqing of the National Institutes of Health Vaccine Research Center, the comprehensive use of cryo-electron microscopy crystal structure analysis, homology modeling and virus single-genome sequencing technology to systematically study the J038 lineage broad-spectrum neutralizing antibody in SHIV - infected rhesus monkeys J038 antibody was found to bind to the special " upright " V2 loop of Env , making the broad-spectrum neutralizing antibody more likely to bind to the CD4 -binding region on Env ( Figure 2 ), and revealed the generation and evolution mechanism of a new V2 -specific broad-spectrum neutralizing antibody, that is, the broad-spectrum of such broad-spectrum neutralizing antibodies is in the process of evolutionary maturation through the continuous increase in the envelope The binding area of the protein and its surface polysaccharides was obtained (Fig.
3 ) .
The figure shows the homology modeling analysis of the binding sites of the transition antibodies in each stage of the evolution of the J038 lineage .
The binding interface of polysaccharides .
The analysis at the evolutionary level further shows the significance of this study .
These results are designed to
HIV-1 envelope protein-based novel AIDS vaccine strategy provides ideas
This research work has been supported by the National Key R&D Program ( 2021YFC2301500 ), the National Natural Science Foundation of China ( 3197088882002138 ), the National Science and Technology Pillar Program during the " 13th Five-Year Plan " period ( 2018ZX10731101-001-010 and 2018ZX10731101-002-003 ), etc.
We would also like to express our sincere thanks to the National Center for Vaccine Research, the National Institute of Allergy and Infectious Diseases ( NIAID ), and the cryo-EM facility of the Frederick National Cancer Research Laboratory for their support!
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