Functional and immunochemical cross-reactivity of V2-specific monoclonal antibodies from HIV-1-infected individuals

被引：76

作者：

Gorny, Miroslaw K. ^{[1
]}

Pan, Ruimin ^{[2
]}

Williams, Constance ^{[1
]}

Wang, Xiao-Hong ^{[3
]}

Volsky, Barbara ^{[1
]}

O'Neal, Timothy ^{[1
]}

Spurrier, Brett ^{[2
]}

Sampson, Jared M. ^{[2
]}

Li, Liuzhe ^{[1
]}

Seaman, Michael S. ^{[4
]}

Kong, Xiang-Peng ^{[2
]}

Zolla-Pazner, Susan ^{[1
,3
]}

机构：

[1] NYU, Sch Med, Dept Pathol, New York, NY 10016 USA

[2] NYU, Sch Med, Dept Biochem, New York, NY 10016 USA

[3] Vet Affairs New York Harbor Healthcare Syst, New York, NY 10010 USA

[4] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA

来源：

VIROLOGY | 2012年 / 427卷 / 02期

关键词：

HIV-1; V2; domain; Envelope proteins; Human monoclonal antibodies; HIV neutralizing antibodies; Glycosylation; NEUTRALIZING ANTIBODIES; STRUCTURAL BASIS; V1/V2; DOMAIN; HIV-1; GP120; POTENT NEUTRALIZATION; ENVELOPE GLYCOPROTEIN; STRUCTURE PREDICTION; GLYCOSYLATION SITES; IMMUNE-RESPONSE; V2;

D O I：

10.1016/j.virol.2012.02.003

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

The recent analysis of the first successful RV144 vaccine trial revealed that a high titer of plasma anti-V2 antibodies (Abs) correlated with a decreased risk of HIV-1 infection in vaccine recipients. To understand the mechanism of immune correlates, we studied seven anti-V2 monoclonal Abs (mAbs) developed from HIV-1 infected individuals. The V2 mAbs target conserved epitopes, including the binding site for alpha 4 beta 7 integrin, and are broadly cross-reactive with various gp120 proteins. Preferential usage of the VH1-69 gene by V2 mAbs may depend on selection by the same antigenic structure. Six of seven V2 mAbs weakly neutralized four to eight of the 41 pseudoviruses tested and resistance to neutralization was correlated with longer V2 domains. The data suggest the presence of shared, conserved structural elements in the V2 loop, and these can be used in the design of vaccine immunogens inducing broadly reactive Abs with anti-viral activities. (C) 2012 Elsevier Inc. All rights reserved.

引用

页码：198 / 207

页数：10

共 64 条

[1] ICM - A NEW METHOD FOR PROTEIN MODELING AND DESIGN - APPLICATIONS TO DOCKING AND STRUCTURE PREDICTION FROM THE DISTORTED NATIVE CONFORMATION [J].

ABAGYAN, R ;

TOTROV, M ;

KUZNETSOV, D .

JOURNAL OF COMPUTATIONAL CHEMISTRY, 1994, 15 (05) :488-506

[2] PHENIX:: building new software for automated crystallographic structure determination [J].

Adams, PD ;

Grosse-Kunstleve, RW ;

Hung, LW ;

Ioerger, TR ;

McCoy, AJ ;

Moriarty, NW ;

Read, RJ ;

Sacchettini, JC ;

Sauter, NK ;

Terwilliger, TC .

ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY, 2002, 58 :1948-1954

[3] HIV-1 envelope protein binds to and signals through integrin α4β7, the gut mucosal homing receptor for peripheral T cells [J].

Arthos, James ;

Cicala, Claudia ;

Martinelli, Elena ;

Macleod, Katilyn ;

Van Ryk, Donald ;

Wei, Danlan ;

Xiao, Zhen ;

Veenstra, Timothy D. ;

Conrad, Thomas P. ;

Lempicki, Richard A. ;

McLaughlin, Sherry ;

Pascuccio, Massimiliano ;

Gopaul, Ravindra ;

McNally, Jonathan ;

Cruz, Catherine C. ;

Censoplano, Nina ;

Chung, Eva ;

Reitano, Kristin N. ;

Kottilil, Shyam ;

Goode, Diana J. ;

Fauci, Anthony S. .

NATURE IMMUNOLOGY, 2008, 9 (03) :301-309

[4] Structural Basis of the Cross-Reactivity of Genetically Related Human Anti-HIV-1 mAbs: Implications for Design of V3-Based Immunogens [J].

Burke, Valicia ;

Williams, Constance ;

Sukumaran, Madhav ;

Kim, Seung-Sup ;

Li, Huiguang ;

Wang, Xiao-Hong ;

Gorny, Miroslaw K. ;

Zolla-Pazner, Susan ;

Kong, Xiang-Peng .

STRUCTURE, 2009, 17 (11) :1538-1546

[5] Crystal Structure of Human Antibody 2909 Reveals Conserved Features of Quaternary Structure-Specific Antibodies That Potently Neutralize HIV-1 [J].

Changela, Anita ;

Wu, Xueling ;

Yang, Yongping ;

Zhang, Baoshan ;

Zhu, Jiang ;

Nardone, Glenn A. ;

O'Dell, Sijy ;

Pancera, Marie ;

Gorny, Miroslaw K. ;

Phogat, Sanjay ;

Robinson, James E. ;

Stamatatos, Leonidas ;

Zolla-Pazner, Susan ;

Mascola, John R. ;

Kwong, Peter D. .

JOURNAL OF VIROLOGY, 2011, 85 (06) :2524-2535

[6] Analysis of Memory B Cell Responses and Isolation of Novel Monoclonal Antibodies with Neutralizing Breadth from HIV-1-Infected Individuals [J].

Corti, Davide ;

Langedijk, Johannes P. M. ;

Hinz, Andreas ;

Seaman, Michael S. ;

Vanzetta, Fabrizia ;

Fernandez-Rodriguez, Blanca M. ;

Silacci, Chiara ;

Pinna, Debora ;

Jarrossay, David ;

Balla-Jhagjhoorsingh, Sunita ;

Willems, Betty ;

Zekveld, Maria J. ;

Dreja, Hanna ;

O'Sullivan, Eithne ;

Pade, Corinna ;

Orkin, Chloe ;

Jeffs, Simon A. ;

Montefiori, David C. ;

Davis, David ;

Weissenhorn, Winfried ;

McKnight, Aine ;

Heeney, Jonathan L. ;

Sallusto, Federica ;

Sattentau, Quentin J. ;

Weiss, Robin A. ;

Lanzavecchia, Antonio .

PLOS ONE, 2010, 5 (01)

[7]

DeLano WL, 2002, PYMOL USERS MANUAL

[8] Antibody Recognition of a Highly Conserved Influenza Virus Epitope [J].

Ekiert, Damian C. ;

Bhabha, Gira ;

Elsliger, Marc-Andre ;

Friesen, Robert H. E. ;

Jongeneelen, Mandy ;

Throsby, Mark ;

Goudsmit, Jaap ;

Wilson, Ian A. .

SCIENCE, 2009, 324 (5924) :246-251

[9] Coot:: model-building tools for molecular graphics [J].

Emsley, P ;

Cowtan, K .

ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY, 2004, 60 :2126-2132

[10] Generation of neutralizing human monoclonal antibodies against parvovirus B19 proteins [J].

Gigler, A ;

Dorsch, S ;

Hemauer, A ;

Williams, C ;

Kim, S ;

Young, NS ;

Zolla-Pazner, S ;

Wolf, H ;

Gorny, MK ;

Modrow, S .

JOURNAL OF VIROLOGY, 1999, 73 (03) :1974-1979

← 1 2 3 4 5 6 7 →