Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus

被引：806

作者：

Liao, Hua-Xin ^{[1
,2
,3
]}

Lynch, Rebecca ^{[4
]}

Zhou, Tongqing ^{[4
]}

Gao, Feng ^{[1
,2
,3
]}

Alam, S. Munir ^{[1
,2
,3
]}

Boyd, Scott D. ^{[5
]}

Fire, Andrew Z. ^{[5
]}

Roskin, Krishna M. ^{[5
]}

Schramm, Chaim A. ^{[6
]}

Zhang, Zhenhai ^{[6
]}

Zhu, Jiang ^{[4
]}

Shapiro, Lawrence ^{[4
,6
]}

Mullikin, James C. ^{[7
,8
]}

Gnanakaran, S. ^{[9
]}

Hraber, Peter ^{[9
]}

Wiehe, Kevin ^{[1
,2
,3
]}

Kelsoe, Garnett ^{[1
,2
,3
]}

Yang, Guang ^{[1
,2
,3
]}

Xia, Shi-Mao ^{[1
,2
,3
]}

Montefiori, David C. ^{[1
,2
,3
]}

Parks, Robert ^{[1
,2
,3
]}

Lloyd, Krissey E. ^{[1
,2
,3
]}

Scearce, Richard M. ^{[1
,2
,3
]}

Soderberg, Kelly A. ^{[1
,2
,3
]}

Cohen, Myron ^{[10
,11
,12
]}

Kamanga, Gift ^{[13
]}

Louder, Mark K. ^{[4
]}

Tran, Lillian M. ^{[4
]}

Chen, Yue ^{[1
,2
,3
]}

Cai, Fangping ^{[1
,2
,3
]}

Chen, Sheri ^{[1
,2
,3
]}

Moquin, Stephanie ^{[4
]}

Du, Xiulian ^{[4
]}

Joyce, M. Gordon ^{[4
]}

Srivatsan, Sanjay ^{[4
]}

Zhang, Baoshan ^{[4
]}

Zheng, Anqi ^{[4
]}

Shaw, George M. ^{[14
,15
]}

Hahn, Beatrice H. ^{[14
,15
]}

Kepler, Thomas B. ^{[16
]}

Korber, Bette T. M. ^{[9
]}

Kwong, Peter D. ^{[4
]}

Mascola, John R. ^{[4
]}

Haynes, Barton F. ^{[1
,2
,3
]}

机构：

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

[2] Duke Univ, Sch Med, Dept Immunol, Human Vaccine Inst, Durham, NC 27710 USA

[3] Duke Ctr HIV AIDS Vaccine Immunol & Immunogen Dis, Durham, NC 27710 USA

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

[5] Stanford Univ, Dept Pathol, Palo Alto, CA 94305 USA

[6] Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA

[7] NIH, NISC Comparat Sequencing Program, Bethesda, MD 20892 USA

[8] NHGRI, NIH Intramural Sequencing Ctr, NIH, Bethesda, MD 20892 USA

[9] Los Alamos Natl Lab, Div Theoret, Los Alamos, NM 87544 USA

[10] Univ N Carolina, Dept Med, Chapel Hill, NC 27599 USA

[11] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA

[12] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA

[13] Univ North Carolina Project, Kamuzu Cent Hosp, Lilongwe, Malawi

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

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

[16] Boston Univ, Dept Microbiol, Boston, MA 02215 USA

来源：

NATURE | 2013年 / 496卷 / 7446期

基金：

美国国家卫生研究院;

关键词：

B-CELL RESPONSES; HUMAN MONOCLONAL-ANTIBODIES; IN-SITU PROTEOLYSIS; CD4; BINDING-SITE; CONFORMATIONAL EPITOPE; POTENT NEUTRALIZATION; ENVELOPE GLYCOPROTEIN; SUBTYPE-B; CRYSTALLIZATION; EVOLUTION;

D O I：

10.1038/nature12053

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：

Current human immunodeficiency virus-1 (HIV-1) vaccines elicit strain-specific neutralizing antibodies. However, cross-reactive neutralizing antibodies arise in approximately 20% of HIV-1-infected individuals, and details of their generation could provide a blueprint for effective vaccination. Here we report the isolation, evolution and structure of a broadly neutralizing antibody from an African donor followed from the time of infection. The mature antibody, CH103, neutralized approximately 55% of HIV-1 isolates, and its co-crystal structure with the HIV-1 envelope protein gp120 revealed a new loop-based mechanism of CD4-binding-site recognition. Virus and antibody gene sequencing revealed concomitant virus evolution and antibody maturation. Notably, the unmutated common ancestor of the CH103 lineage avidly bound the transmitted/founder HIV-1 envelope glycoprotein, and evolution of antibody neutralization breadth was preceded by extensive viral diversification in and near the CH103 epitope. These data determine the viral and antibody evolution leading to induction of a lineage of HIV-1 broadly neutralizing antibodies, and provide insights into strategies to elicit similar antibodies by vaccination.

引用

页码：469 / +

页数：11

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