Rational Design of Envelope Identifies Broadly Neutralizing Human Monoclonal Antibodies to HIV-1

被引：1401

作者：

Wu, Xueling ^{[1
]}

Yang, Zhi-Yong ^{[1
]}

Li, Yuxing ^{[1
]}

Hogerkorp, Carl-Magnus ^{[1
]}

Schief, William R. ^{[4
]}

Seaman, Michael S. ^{[5
]}

Zhou, Tongqing ^{[1
]}

Schmidt, Stephen D. ^{[1
]}

Wu, Lan ^{[1
]}

Xu, Ling ^{[1
]}

Longo, Nancy S. ^{[1
]}

McKee, Krisha ^{[1
]}

O'Dell, Sijy ^{[1
]}

Louder, Mark K. ^{[1
]}

Wycuff, Diane L. ^{[1
]}

Feng, Yu ^{[1
]}

Nason, Martha ^{[2
]}

Doria-Rose, Nicole ^{[3
]}

Connors, Mark ^{[3
]}

Kwong, Peter D. ^{[1
]}

Roederer, Mario ^{[1
]}

Wyatt, Richard T. ^{[1
]}

Nabel, Gary J. ^{[1
]}

Mascola, John R. ^{[1
]}

机构：

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

[2] NIAID, Biostat Res Branch, Div Clin Res, NIH, Bethesda, MD 20892 USA

[3] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA

[4] Univ Washington, Dept Biochem, Seattle, WA 98195 USA

[5] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA

来源：

SCIENCE | 2010年 / 329卷 / 5993期

关键词：

TYPE-1; INFECTION; HIGH-AFFINITY; VIRUS; GP120; BREADTH; GLYCOPROTEIN; INDIVIDUALS; PANEL; IMMUNOGENICITY; SPECIFICITIES;

D O I：

10.1126/science.1187659

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：

Cross-reactive neutralizing antibodies (NAbs) are found in the sera of many HIV-1-infected individuals, but the virologic basis of their neutralization remains poorly understood. We used knowledge of HIV-1 envelope structure to develop antigenically resurfaced glycoproteins specific for the structurally conserved site of initial CD4 receptor binding. These probes were used to identify sera with NAbs to the CD4-binding site (CD4bs) and to isolate individual B cells from such an HIV-1-infected donor. By expressing immunoglobulin genes from individual cells, we identified three monoclonal antibodies, including a pair of somatic variants that neutralized over 90% of circulating HIV-1 isolates. Exceptionally broad HIV-1 neutralization can be achieved with individual antibodies targeted to the functionally conserved CD4bs of glycoprotein 120, an important insight for future HIV-1 vaccine design.

引用

页码：856 / 861

页数：6

共 33 条

[21] Factors Associated with the Development of Cross-Reactive Neutralizing Antibodies during Human Immunodeficiency Virus Type 1 Infection
Sather, D. Noah
Armann, Jakob
Ching, Lance K.
Mavrantoni, Angeliki
Sellhorn, George
Caldwell, Zachary
Yu, Xuesong
Wood, Blake
Self, Steve
Kalams, Spyros
Stamatatos, Leonidas
[J]. JOURNAL OF VIROLOGY, 2009, 83 (02) : 757 - 769
[22] Broad diversity of neutralizing antibodies isolated from memory B cells in HIV-infected individuals
Scheid, Johannes F.
Mouquet, Hugo
Feldhahn, Niklas
Seaman, Michael S.
Velinzon, Klara
Pietzsch, John
Ott, Rene G.
Anthony, Robert M.
Zebroski, Henry
Hurley, Arlene
Phogat, Adhuna
Chakrabarti, Bimal
Li, Yuxing
Connors, Mark
Pereyra, Florencia
Walker, Bruce D.
Wardemann, Hedda
Ho, David
Wyatt, Richard T.
Mascola, John R.
Ravetch, Jeffrey V.
Nussenzweig, Michel C.
[J]. NATURE, 2009, 458 (7238) : 636 - 640
[23] Tiered Categorization of a Diverse Panel of HIV-1 Env Pseudoviruses for Assessment of Neutralizing Antibodies
Seaman, Michael S.
Janes, Holly
Hawkins, Natalie
Grandpre, Lauren E.
Devoy, Colleen
Giri, Ayush
Coffey, Rory T.
Harris, Linda
Wood, Blake
Daniels, Marcus G.
Bhattacharya, Tanmoy
Lapedes, Alan
Polonis, Victoria R.
McCutchan, Francine E.
Gilbert, Peter B.
Self, Steve G.
Korber, Bette T.
Montefiori, David C.
Mascola, John R.
[J]. JOURNAL OF VIROLOGY, 2010, 84 (03) : 1439 - 1452
[24] In Vivo gp41 Antibodies Targeting the 2F5 Monoclonal Antibody Epitope Mediate Human Immunodeficiency Virus Type 1 Neutralization Breadth
Shen, Xiaoying
Parks, Robert J.
Montefiori, David C.
Kirchherr, Jennifer L.
Keele, Brandon F.
Decker, Julie M.
Blattner, William A.
Gao, Feng
Weinhold, Kent J.
Hicks, Charles B.
Greenberg, Michael L.
Hahn, Beatrice H.
Shaw, George M.
Haynes, Barton F.
Tomaras, Georgia D.
[J]. JOURNAL OF VIROLOGY, 2009, 83 (08) : 3617 - 3625
[25] Human Immunodeficiency Virus Type 1 Elite Neutralizers: Individuals with Broad and Potent Neutralizing Activity Identified by Using a High-Throughput Neutralization Assay together with an Analytical Selection Algorithm
Simek, Melissa D.
Rida, Wasima
Priddy, Frances H.
Pung, Pham
Carrow, Emily
Laufer, Dagna S.
Lehrman, Jennifer K.
Boaz, Mark
Tarragona-Fiol, Tony
Miiro, George
Birungi, Josephine
Pozniak, Anton
McPhee, Dale A.
Manigart, Olivier
Karita, Etienne
Inwoley, Andre
Jaoko, Walter
DeHovitz, Jack
Bekker, Linda-Gail
Pitisuttithum, Punnee
Paris, Robert
Walker, Laura M.
Poignard, Pascal
Wrin, Terri
Fast, Patricia E.
Burton, Dennis R.
Koff, Wayne C.
[J]. JOURNAL OF VIROLOGY, 2009, 83 (14) : 7337 - 7348
[26] Lack of neutralizing antibody response to HIV-1 predisposes to superinfection
Smith, Davey M.
Strain, Matthew C.
Frost, Simon D. W.
Pillai, Satish K.
Wong, Joseph K.
Wrin, Terri
Liu, Yang
Petropolous, Christos J.
Daar, Eric S.
Little, Susan J.
Richman, Douglas D.
[J]. VIROLOGY, 2006, 355 (01) : 1 - 5
[27] Neutralizing antibodies generated during natural HIV-1 infection: good news for an HIV-1 vaccine?
Stamatatos, Leonidas
Morris, Lynn
Burton, Dennis R.
Mascola, John R.
[J]. NATURE MEDICINE, 2009, 15 (08) : 866 - 870
[28] Broad and Potent Neutralizing Antibodies from an African Donor Reveal a New HIV-1 Vaccine Target
Walker, Laura M.
Phogat, Sanjay K.
Chan-Hui, Po-Ying
Wagner, Denise
Phung, Pham
Goss, Julie L.
Wrin, Terri
Simek, Melissa D.
Fling, Steven
Mitcham, Jennifer L.
Lehrman, Jennifer K.
Priddy, Frances H.
Olsen, Ole A.
Frey, Steven M.
Hammond, Phillip W.
Kaminsky, Stephen
Zamb, Timothy
Moyle, Matthew
Koff, Wayne C.
Poignard, Pascal
Burton, Dennis R.
[J]. SCIENCE, 2009, 326 (5950) : 285 - 289
[29] Rapid cloning of high-affinity human monoclonal antibodies against influenza virus
Wrammert, Jens
Smith, Kenneth
Miller, Joe
Langley, William A.
Kokko, Kenneth
Larsen, Christian
Zheng, Nai-Ying
Mays, Israel
Garman, Lori
Helms, Christina
James, Judith
Air, Gillian M.
Capra, J. Donald
Ahmed, Rafi
Wilson, Patrick C.
[J]. NATURE, 2008, 453 (7195) : 667 - U10
[30] The antigenic structure of the HIV gp120 envelope glycoprotein
Wyatt, R
Kwong, PD
Desjardins, E
Sweet, RW
Robinson, J
Hendrickson, WA
Sodroski, JG
[J]. NATURE, 1998, 393 (6686) : 705 - 711

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