Open AccessDevelopment of Neutralization Breadth against Diverse HIV‐1 by Increasing Ab–Ag Interface on V2
Author(s) -
Gao Nan,
Gai Yanxin,
Meng Lina,
Wang Chu,
Wang Wei,
Li Xiaojun,
Gu Tiejun,
Louder Mark K.,
DoriaRose 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.,
Mascola John R.,
Qin Chuan,
Zhou Tongqing,
Yu Xianghui,
Gao Feng
Publication year - 2022
Publication title -
advanced science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.388
H-Index - 100
ISSN - 2198-3844
DOI - 10.1002/advs.202200063
Subject(s) - glycan , neutralization , antibody , lineage (genetic) , glycoprotein , biology , virology , germline , human immunodeficiency virus (hiv) , immune escape , simian immunodeficiency virus , genetics , gene , immune system
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.