Recapitulation of HIV-1 Env-antibody coevolution in macaques leading to neutralization breadth

被引：46

作者：

Roark, Ryan S. ^{[1
,2
]}

Li, Hui ^{[1
,2
]}

Williams, Wilton B. ^{[3
,4
]}

Chug, Hema ^{[5
,6
]}

Mason, Rosemarie D. ^{[7
]}

Gorman, Jason ^{[7
]}

Wang, Shuyi ^{[1
,2
]}

Lee, Fang-Hua ^{[1
,2
]}

Rando, Juliette ^{[1
,2
]}

Bonsignori, Mattia ^{[3
,4
]}

Hwang, Kwan-Ki ^{[3
]}

Saunders, Kevin O. ^{[3
,8
,9
]}

Wiehe, Kevin ^{[3
,4
]}

Moody, M. Anthony ^{[3
,8
,10
]}

Hraber, Peter T. ^{[11
]}

Wagh, Kshitij ^{[11
]}

Giorgi, Elena E. ^{[11
]}

Russell, Ronnie M. ^{[1
,2
]}

Bibollet-Ruche, Frederic ^{[1
,2
]}

Liu, Weimin ^{[1
,2
]}

Connell, Jesse ^{[1
,2
]}

Smith, Andrew G. ^{[1
,2
]}

DeVoto, Julia ^{[1
,2
]}

Murphy, Alexander, I ^{[1
,2
]}

Smith, Jessica ^{[1
,2
]}

Ding, Wenge ^{[1
,2
]}

Zhao, Chengyan ^{[1
,2
]}

Chohan, Neha ^{[1
,2
]}

Okumura, Maho ^{[1
,2
]}

Rosario, Christina ^{[1
,2
]}

Ding, Yu ^{[1
,2
]}

Lindemuth, Emily ^{[1
,2
]}

Bauer, Anya M. ^{[1
,2
]}

Bar, Katharine J. ^{[1
,2
]}

Ambrozak, David ^{[7
]}

Chao, Cara W. ^{[7
]}

Chuang, Gwo-Yu ^{[7
]}

Geng, Hui ^{[7
]}

Lin, Bob C. ^{[7
]}

Louder, Mark K. ^{[7
]}

Nguyen, Richard ^{[7
]}

Zhang, Baoshan ^{[7
]}

Lewis, Mark G. ^{[12
]}

Raymond, Donald D. ^{[5
,6
]}

Doria-Rose, Nicole A. ^{[7
]}

Schramm, Chaim A. ^{[7
]}

Douek, Daniel C. ^{[7
]}

Roederer, Mario ^{[7
]}

Kepler, Thomas B. ^{[13
,14
]}

Kelsoe, Garnett ^{[3
,8
,9
]}

机构：

[1] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA

[2] Univ Penn, Perelman Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA

[3] Duke Univ, Duke Human Vaccine Inst, Sch Med, Durham, NC 27710 USA

[4] Duke Univ, Dept Med, Sch Med, Durham, NC 27710 USA

[5] Boston Childrens Hosp, Lab Mol Med, Boston, MA 02115 USA

[6] Harvard Med Sch, Boston, MA 02115 USA

[7] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA

[8] Duke Univ, Dept Immunol, Sch Med, Durham, NC 27710 USA

[9] Duke Univ, Dept Surg, Sch Med, Durham, NC 27710 USA

[10] Duke Univ, Dept Pediat, Sch Med, Durham, NC 27710 USA

[11] Los Alamos Natl Lab, Theoret Biol & Biophys, Los Alamos, NM 87545 USA

[12] Bioqual Inc, Rockville, MD 20850 USA

[13] Boston Univ, Dept Microbiol, Sch Med, Boston, MA 02118 USA

[14] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA

[15] Harvard Med Sch, Howard Hughes Med Inst, Boston, MA 02115 USA

来源：

SCIENCE | 2021年 / 371卷 / 6525期

关键词：

HUMAN MONOCLONAL-ANTIBODIES; B-CELL-LINEAGE; AFFINITY MATURATION; RHESUS MACAQUES; SUBTYPE-B; V2; APEX; ENVELOPE; BROAD; BINDING; GP120;

D O I：

10.1126/science.abd2638

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Neutralizing antibodies elicited by HIV-1 coevolve with viral envelope proteins (Env) in distinctive patterns, in some cases acquiring substantial breadth. We report that primary HIV-1 envelope proteins-when expressed by simian-human immunodeficiency viruses in rhesus macaques-elicited patterns of Env-antibody coevolution very similar to those in humans, including conserved immunogenetic, structural, and chemical solutions to epitope recognition and precise Env-amino acid substitutions, insertions, and deletions leading to virus persistence. The structure of one rhesus antibody, capable of neutralizing 49% of a 208-strain panel, revealed a V2 apex mode of recognition like that of human broadly neutralizing antibodies (bNAbs) PGT145 and PCT64-35S. Another rhesus antibody bound the CD4 binding site by CD4 mimicry, mirroring human bNAbs 8ANC131, CH235, and VRC01. Virus-antibody coevolution in macaques can thus recapitulate developmental features of human bNAbs, thereby guiding HIV-1 immunogen design.

引用

页码：142 / +

页数：20

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