Advanced Science (May 2022)
Development of Neutralization Breadth against Diverse HIV‐1 by Increasing Ab–Ag Interface on V2
- Nan Gao,
- Yanxin Gai,
- Lina Meng,
- Chu Wang,
- Wei Wang,
- Xiaojun Li,
- Tiejun Gu,
- Mark K. Louder,
- Nicole A. Doria‐Rose,
- Kevin Wiehe,
- Alexandra F. Nazzari,
- Adam S. Olia,
- Jason Gorman,
- Reda Rawi,
- Wenmin Wu,
- Clayton Smith,
- Htet Khant,
- Natalia de Val,
- Bin Yu,
- Junhong Luo,
- Haitao Niu,
- Yaroslav Tsybovsky,
- Huaxin Liao,
- Thomas B. Kepler,
- Peter D. Kwong,
- John R. Mascola,
- Chuan Qin,
- Tongqing Zhou,
- Xianghui Yu,
- Feng Gao
Affiliations
- Nan Gao
- National Engineering Laboratory for AIDS Vaccine, School of Life Sciences Jilin University Changchun Jilin Province 130012 China
- Yanxin Gai
- National Engineering Laboratory for AIDS Vaccine, School of Life Sciences Jilin University Changchun Jilin Province 130012 China
- Lina Meng
- National Engineering Laboratory for AIDS Vaccine, School of Life Sciences Jilin University Changchun Jilin Province 130012 China
- Chu Wang
- National Engineering Laboratory for AIDS Vaccine, School of Life Sciences Jilin University Changchun Jilin Province 130012 China
- Wei Wang
- Institute of Laboratory Animal Science Chinese Academy of Medical Sciences Beijing 100021 China
- Xiaojun Li
- Department of Medicine Duke University School of Medicine Durham NC 27710 USA
- Tiejun Gu
- National Engineering Laboratory for AIDS Vaccine, School of Life Sciences Jilin University Changchun Jilin Province 130012 China
- Mark K. Louder
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases National Institutes of Health Bethesda MD 20892 USA
- Nicole A. Doria‐Rose
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases National Institutes of Health Bethesda MD 20892 USA
- Kevin Wiehe
- Duke University Human Vaccine Institute Duke University School of Medicine Durham NC 27710 USA
- Alexandra F. Nazzari
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases National Institutes of Health Bethesda MD 20892 USA
- Adam S. Olia
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases National Institutes of Health Bethesda MD 20892 USA
- Jason Gorman
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases National Institutes of Health Bethesda MD 20892 USA
- Reda Rawi
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases National Institutes of Health Bethesda MD 20892 USA
- Wenmin Wu
- Cancer Research Technology Program, Frederick National Laboratory for Cancer Research Leidos Biomedical Research Inc. Frederick MD 21701 USA
- Clayton Smith
- Cancer Research Technology Program, Frederick National Laboratory for Cancer Research Leidos Biomedical Research Inc. Frederick MD 21701 USA
- Htet Khant
- Cancer Research Technology Program, Frederick National Laboratory for Cancer Research Leidos Biomedical Research Inc. Frederick MD 21701 USA
- Natalia de Val
- Cancer Research Technology Program, Frederick National Laboratory for Cancer Research Leidos Biomedical Research Inc. Frederick MD 21701 USA
- Bin Yu
- National Engineering Laboratory for AIDS Vaccine, School of Life Sciences Jilin University Changchun Jilin Province 130012 China
- Junhong Luo
- Institute of Molecular and Medical Virology, School of Medicine Jinan University Guangzhou Guangdong Province 510632 China
- Haitao Niu
- Institute of Molecular and Medical Virology, School of Medicine Jinan University Guangzhou Guangdong Province 510632 China
- Yaroslav Tsybovsky
- Cancer Research Technology Program, Frederick National Laboratory for Cancer Research Leidos Biomedical Research Inc. Frederick MD 21701 USA
- Huaxin Liao
- Institute of Molecular and Medical Virology, School of Medicine Jinan University Guangzhou Guangdong Province 510632 China
- Thomas B. Kepler
- Department of Microbiology Boston University Boston MA 02215 USA
- Peter D. Kwong
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases National Institutes of Health Bethesda MD 20892 USA
- John R. Mascola
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases National Institutes of Health Bethesda MD 20892 USA
- Chuan Qin
- Institute of Laboratory Animal Science Chinese Academy of Medical Sciences Beijing 100021 China
- Tongqing Zhou
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases National Institutes of Health Bethesda MD 20892 USA
- Xianghui Yu
- National Engineering Laboratory for AIDS Vaccine, School of Life Sciences Jilin University Changchun Jilin Province 130012 China
- Feng Gao
- National Engineering Laboratory for AIDS Vaccine, School of Life Sciences Jilin University Changchun Jilin Province 130012 China
- DOI
- https://doi.org/10.1002/advs.202200063
- Journal volume & issue
-
Vol. 9,
no. 15
pp. n/a – n/a
Abstract
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.
Keywords
- antibody evolution
- broadly neutralizing antibodies
- humoral immunity
- nonhuman primates
- simian/human immunodeficiency virus
- virus variation
