Maturation Pathway from Germline to Broad HIV-1 Neutralizer of a CD4-Mimic Antibody

被引：249

作者：

Bonsignori, Mattia ^{[1
,2
]}

Zhou, Tongqing ^{[3
]}

Sheng, Zizhang ^{[4
,5
]}

Chen, Lei ^{[3
]}

Gao, Feng ^{[1
,2
]}

Joyce, M. Gordon ^{[3
]}

Ozorowski, Gabriel ^{[6
,7
,8
]}

Chuang, Gwo-Yu ^{[3
]}

Schramm, Chaim A. ^{[4
,5
]}

Wiehe, Kevin ^{[1
,2
]}

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

Bradley, Todd ^{[1
]}

Gladden, Morgan A. ^{[1
]}

Hwang, Kwan-Ki ^{[1
]}

Iyengar, Sheelah ^{[1
]}

Kumar, Amit ^{[1
]}

Lu, Xiaozhi ^{[1
]}

Luo, Kan ^{[1
]}

Mangiapani, Michael C. ^{[1
]}

Parks, Robert J. ^{[1
]}

Song, Hongshuo ^{[1
]}

Acharya, Priyamvada ^{[3
]}

Bailer, Robert T. ^{[3
]}

Cao, Allen ^{[3
]}

Druz, Aliaksandr ^{[3
]}

Georgiev, Ivelin S. ^{[3
,9
,10
,11
]}

Kwon, Young D. ^{[3
]}

Louder, Mark K. ^{[3
]}

Zhang, Baoshan ^{[3
]}

Zheng, Anqi ^{[3
]}

Hill, Brenna J. ^{[3
]}

Kong, Rui ^{[3
]}

Soto, Cinque ^{[3
]}

Mullikin, James C. ^{[12
]}

Douek, Daniel C. ^{[3
]}

Montefiori, David C. ^{[1
,13
,14
,15
]}

Moody, Michael A. ^{[1
,14
,15
]}

Shaw, George M. ^{[16
,17
]}

Hahn, Beatrice H. ^{[16
,17
]}

Kelsoe, Garnett ^{[1
,15
]}

Hraber, Peter T. ^{[18
]}

Korber, Bette T. ^{[18
]}

Boyd, Scott D. ^{[19
]}

Fire, Andrew Z. ^{[19
]}

Kepler, Thomas B. ^{[20
,21
]}

Shapiro, Lawrence ^{[3
,4
,5
]}

Ward, Andrew B. ^{[6
,7
,8
]}

Mascola, John R. ^{[3
]}

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

Kwong, Peter D. ^{[3
]}

机构：

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

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

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

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

[5] Columbia Univ, Dept Syst Biol, New York, NY 10032 USA

[6] Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA

[7] Scripps Res Inst, CAVD, IAVI Neutralizing Antibody Ctr, La Jolla, CA 92037 USA

[8] Scripps Res Inst, Ctr HIV AIDS Vaccine Immunol & Immunogen Discover, La Jolla, CA 92037 USA

[9] Vanderbilt Univ, Med Ctr, Dept Pathol Microbiol & Immunol, Nashville, TN 37232 USA

[10] Vanderbilt Univ, Dept Elect Engn & Comp Sci, Nashville, TN 37232 USA

[11] Vanderbilt Univ, Med Ctr, Vanderbilt Vaccine Ctr, Nashville, TN 37232 USA

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

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

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

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

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

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

[18] Los Alamos Natl Lab, POB 1663, Los Alamos, NM 87544 USA

[19] Stanford Sch Med, Dept Pathol, Palo Alto, CA 94305 USA

[20] Boston Univ, Dept Microbiol, Boston, MA 02118 USA

[21] Boston Univ, Dept Math & Stat, Boston, MA 02118 USA

[22] Duke Univ, Sch Med, Duke Global Hlth Inst, Durham, NC 27710 USA

来源：

CELL | 2016年 / 165卷 / 02期

关键词：

HUMAN MONOCLONAL-ANTIBODIES; B-CELL RECEPTORS; VACCINE DEVELOPMENT; IMMUNOGEN DESIGN; FOUNDER VIRUS; AUTOREACTIVITY; INFECTION; INDUCTION; MEMBRANE; BINDING;

D O I：

10.1016/j.cell.2016.02.022

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Antibodies with ontogenies from V(H)1-2 or V(H)1-46-germline genes dominate the broadly neutralizing response against the CD4-binding site (CD4bs) on HIV-1. Here, we define with longitudinal sampling from time-of-infection the development of a V(H)1-46-derived antibody lineage that matured to neutralize 90% of HIV-1 isolates. Structures of lineage antibodies CH235 (week 41 from time-of-infection, 18% breadth), CH235.9 (week 152, 77%), and CH235.12 (week 323, 90%) demonstrated the maturing epitope to focus on the conformationally invariant portion of the CD4bs. Similarities between CH235 lineage and five unrelated CD4bs lineages in epitope focusing, length-of-time to develop breadth, and extraordinary level of somatic hypermutation suggested commonalities in maturation among all CD4bs antibodies. Fortunately, the required CH235-lineage hypermutation appeared substantially guided by the intrinsic mutability of the V(H)1-46 gene, which closely resembled V(H)1-2. We integrated our CH235-lineage findings with a second broadly neutralizing lineage and HIV-1 co-evolution to suggest a vaccination strategy for inducing both lineages.

引用

页码：449 / 463

页数：15

共 44 条

[1] The role of antibody polyspecificity and lipid reactivity in binding of broadly neutralizing anti-HIV-1 envelope human monoclonal antibodies 2F5 and 4E10 to glycoprotein 41 membrane proximal envelope epitopes [J].

Alam, S. Munir ;

McAdams, Mildred ;

Boren, David ;

Rak, Michael ;

Scearce, Richard M. ;

Gao, Feng ;

Camacho, Zenaido T. ;

Gewirth, Daniel ;

Kelsoe, Garnett ;

Chen, Pojen ;

Haynes, Barton F. .

JOURNAL OF IMMUNOLOGY, 2007, 178 (07) :4424-4435

[2] Role of HIV membrane in neutralization by two broadly neutralizing antibodies [J].

Alam, S. Munir ;

Morelli, Marco ;

Dennison, S. Moses ;

Liao, Hua-Xin ;

Zhang, Ruijun ;

Xia, Shi-Mao ;

Rits-Volloch, Sophia ;

Sun, Li ;

Harrison, Stephen C. ;

Haynes, Barton F. ;

Chen, Bing .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (48) :20234-20239

[3] An autoreactive antibody from an SLE/HIV-1 individual broadly neutralizes HIV-1 [J].

Bonsignori, Mattia ;

Wiehe, Kevin ;

Grimm, Sebastian K. ;

Lynch, Rebecca ;

Yang, Guang ;

Kozink, Daniel M. ;

Perrin, Florence ;

Cooper, Abby J. ;

Hwang, Kwan-Ki ;

Chen, Xi ;

Liu, Mengfei ;

McKee, Krisha ;

Parks, Robert J. ;

Eudailey, Joshua ;

Wang, Minyue ;

Clowse, Megan ;

Criscione-Schreiber, Lisa G. ;

Moody, M. Anthony ;

Ackerman, Margaret E. ;

Boyd, Scott D. ;

Gao, Feng ;

Kelsoe, Garnett ;

Verkoczy, Laurent ;

Tomaras, Georgia D. ;

Liao, Hua-Xin ;

Kepler, Thomas B. ;

Montefiori, David C. ;

Mascola, John R. ;

Haynes, Barton F. .

JOURNAL OF CLINICAL INVESTIGATION, 2014, 124 (04) :1835-1843

[4] HIV-1 antibodies from infection and vaccination: insights for guiding vaccine design [J].

Bonsignori, Mattia ;

Alam, S. Munir ;

Liao, Hua-Xin ;

Verkoczy, Laurent ;

Tomaras, Georgia D. ;

Haynes, Barton F. ;

Moody, M. Anthony .

TRENDS IN MICROBIOLOGY, 2012, 20 (11) :532-539

[5] Analysis of a Clonal Lineage of HIV-1 Envelope V2/V3 Conformational Epitope-Specific Broadly Neutralizing Antibodies and Their Inferred Unmutated Common Ancestors [J].

Bonsignori, Mattia ;

Hwang, Kwan-Ki ;

Chen, Xi ;

Tsao, Chun-Yen ;

Morris, Lynn ;

Gray, Elin ;

Marshall, Dawn J. ;

Crump, John A. ;

Kapiga, Saidi H. ;

Sam, Noel E. ;

Sinangil, Faruk ;

Pancera, Marie ;

Yang Yongping ;

Zhang, Baoshan ;

Zhu, Jiang ;

Kwong, Peter D. ;

O'Dell, Sijy ;

Mascola, John R. ;

Wu, Lan ;

Nabel, Gary J. ;

Phogat, Sanjay ;

Seaman, Michael S. ;

Whitesides, John F. ;

Moody, M. Anthony ;

Kelsoe, Garnett ;

Yang, Xinzhen ;

Sodroski, Joseph ;

Shaw, George M. ;

Montefiori, David C. ;

Kepler, Thomas B. ;

Tomaras, Georgia D. ;

Alam, S. Munir ;

Liao, Hua-Xin ;

Haynes, Barton F. .

JOURNAL OF VIROLOGY, 2011, 85 (19) :9998-10009

[6] Measurement and Clinical Monitoring of Human Lymphocyte Clonality by Massively Parallel V-D-J Pyrosequencing [J].

Boyd, Scott D. ;

Marshall, Eleanor L. ;

Merker, Jason D. ;

Maniar, Jay M. ;

Zhang, Lyndon N. ;

Sahaf, Bita ;

Jones, Carol D. ;

Simen, Birgitte B. ;

Hanczaruk, Bozena ;

Nguyen, Khoa D. ;

Nadeau, Kari C. ;

Egholm, Michael ;

Miklos, David B. ;

Zehnder, James L. ;

Fire, Andrew Z. .

SCIENCE TRANSLATIONAL MEDICINE, 2009, 1 (12)

[7] Immunization for HIV-1 Broadly Neutralizing Antibodies in Human Ig Knockin Mice [J].

Dosenovic, Pia ;

von Boehmer, Lotta ;

Escolano, Amelia ;

Jardine, Joseph ;

Freund, Natalia T. ;

Gitlin, Alexander D. ;

McGuire, Andrew T. ;

Kulp, Daniel W. ;

Oliveira, Thiago ;

Scharf, Louise ;

Pietzsch, John ;

Gray, Matthew D. ;

Cupo, Albert ;

van Gils, Marit J. ;

Yao, Kai-Hui ;

Liu, Cassie ;

Gazumyan, Anna ;

Seaman, Michael S. ;

Bjoerkman, Pamela J. ;

Sanders, Rogier W. ;

Moore, John P. ;

Stamatatos, Leonidas ;

Schief, William R. ;

Nussenzweig, Michel C. .

CELL, 2015, 161 (07) :1505-1515

[8]

Felsenstein J., 2005, PHYLIP (phylogeny inference package) version 3.6

[9] KINETIC MATURATION OF AN IMMUNE-RESPONSE [J].

FOOTE, J ;

MILSTEIN, C .

NATURE, 1991, 352 (6335) :530-532

[10] Cooperation of B Cell Lineages in Induction of HIV-1-Broadly Neutralizing Antibodies [J].

Gao, Feng ;

Bonsignori, Mattia ;

Liao, Hua-Xin ;

Kumar, Amit ;

Xia, Shi-Mao ;

Lu, Xiaozhi ;

Cai, Fangping ;

Hwang, Kwan-Ki ;

Song, Hongshuo ;

Zhou, Tongqing ;

Lynch, Rebecca M. ;

Alam, S. Munir ;

Moody, M. Anthony ;

Ferrari, Guido ;

Berrong, Mark ;

Kelsoe, Garnett ;

Shaw, George M. ;

Hahn, Beatrice H. ;

Montefiori, David C. ;

Kamanga, Gift ;

Cohen, Myron S. ;

Hraber, Peter ;

Kwong, Peter D. ;

Korber, Bette T. ;

Mascola, John R. ;

Kepler, Thomas B. ;

Haynes, Barton F. .

CELL, 2014, 158 (03) :481-491

← 1 2 3 4 5 →