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Development of Neutralization Breadth against Diverse HIV-1 by Increasing Ab-Ag Interface on V2

  1. Author:
    Gao, Nan
    Gai, Yanxin
    Meng, Lina
    Wang, Chu
    Wang, Wei
    Li, Xiaojun
    Gu, Tiejun
    Louder, Mark K
    Doria-Rose, Nicole A
    Wiehe, Kevin
    Nazzari, Alexandra F
    Olia, Adam S
    Gorman, Jason
    Rawi, Reda
    Wu, Wenmin
    Smith, Clayton
    Khant, Htet
    de Val, Natalia
    Yu, Bin
    Luo, Junhong
    Niu, Haitao
    Tsybovsky, Yaroslav
    Liao, Huaxin
    Kepler, Thomas B
    Kwong, Peter D [ORCID]
    Mascola, John R
    Qin, Chuan
    Zhou, Tongqing [ORCID]
    Yu, Xianghui
    Gao, Feng [ORCID]

  2. Author Address

    National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, Jilin Province, 130012, China., Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Beijing, 100021, China., Comparative Medicine Center, Peking Union Medical College, Beijing, 100021, China., Department of Medicine, Duke University School of Medicine, Durham, NC, 27710, USA., Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA., Duke University Human Vaccine Institute, Duke University School of Medicine, Durham, NC, 27710, USA., Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc., Frederick, MD, 21701, USA., Institute of Molecular and Medical Virology, School of Medicine, Jinan University, Guangzhou, Guangdong Province, 510632, China., Department of Microbiology, Boston University, Boston, MA, 02215, USA., Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun, Jilin Province, 130012, China.,
    1. Year: 2022
    2. Date: Mar 23
    3. Epub Date: 2022 03 23
  2. Journal: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
    1. Pages: e2200063
  4. Type of Article: Article
  5. Article Number: e2200063
  1. Abstract:

    Understanding maturation pathways of broadly neutralizing antibodies (bnAbs) against HIV-1 can be highly informative for HIV-1 vaccine development. A lineage of J038 bnAbs is now obtained from a long-term SHIV-infected macaque. J038 neutralizes 54% of global circulating HIV-1 strains. Its binding induces a unique "up" conformation for one of the V2 loops in the trimeric envelope glycoprotein and is heavily dependent on glycan, which provides nearly half of the binding surface. Their unmutated common ancestor neutralizes the autologous virus. Continuous maturation enhances neutralization potency and breadth of J038 lineage antibodies via expanding antibody-Env contact areas surrounding the core region contacted by germline-encoded residues. Developmental details and recognition features of J038 lineage antibodies revealed here provide a new pathway for elicitation and maturation of V2-targeting bnAbs. © 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.

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External Sources

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  2. DOI: 10.1002/advs.202200063
  3. PMID: 35319830

Library Notes

  1. Fiscal Year: FY2021-2022
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