Vaccine Induction of Antibodies against a Structurally Heterogeneous Site of Immune Pressure within HIV-1 Envelope Protein Variable Regions 1 and 2

被引：332

作者：

Liao, Hua-Xin ^{[1
]}

Bonsignori, Mattia ^{[1
]}

Alam, S. Munir ^{[1
]}

McLellan, Jason S. ^{[2
]}

Tomaras, Georgia D. ^{[1
]}

Moody, M. Anthony ^{[1
]}

Kozink, Daniel M. ^{[1
]}

Hwang, Kwan-Ki ^{[1
]}

Chen, Xi ^{[1
]}

Tsao, Chun-Yen ^{[1
]}

Liu, Pinghuang ^{[1
]}

Lu, Xiaozhi ^{[1
]}

Parks, Robert J. ^{[1
]}

Montefiori, David C. ^{[1
]}

Ferrari, Guido ^{[1
]}

Pollara, Justin ^{[1
]}

Rao, Mangala ^{[3
]}

Peachman, Kristina K. ^{[3
]}

Santra, Sampa ^{[4
]}

Letvin, Norman L. ^{[4
]}

Karasavvas, Nicos ^{[5
]}

Yang, Zhi-Yong ^{[2
]}

Dai, Kaifan ^{[2
]}

Pancera, Marie ^{[2
]}

Gorman, Jason ^{[2
]}

Wiehe, Kevin ^{[1
]}

Nicely, Nathan I. ^{[1
]}

Rerks-Ngarm, Supachai ^{[6
]}

Nitayaphan, Sorachai ^{[5
]}

Kaewkungwal, Jaranit ^{[7
]}

Pitisuttithum, Punnee

Tartaglia, James ^{[8
]}

Sinangil, Faruk ^{[9
]}

Kim, Jerome H. ^{[3
]}

Michael, Nelson L. ^{[3
]}

Kepler, Thomas B. ^{[10
]}

Kwong, Peter D. ^{[2
]}

Mascola, John R. ^{[2
]}

Nabel, Gary J. ^{[2
]}

Pinter, Abraham ^{[11
]}

Zolla-Pazner, Susan ^{[12
,13
]}

Haynes, Barton F. ^{[1
]}

机构：

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

[2] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA

[3] Walter Reed Army Inst Res, US Mil HIV Res Program, Silver Spring, MD 20910 USA

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

[5] Armed Forces Res Inst Med Sci, US Army Med Component, Dept Retrovirol, Bangkok 10400, Thailand

[6] Minist Publ Hlth, Dept Dis Control, Nonthaburi 11000, Thailand

[7] Mahidol Univ, Fac Trop Med, Ctr Excellence Biomed & Publ Hlth Informat BIOPHI, Bangkok 10400, Thailand

[8] Sanofi Pasteur, Swiftwater, PA 18370 USA

[9] Global Solut Infect Dis, San Francisco, CA 94080 USA

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

[11] Univ Med & Dent New Jersey, New Jersey Med Sch, Publ Hlth Res Inst Ctr, Newark, NJ 07103 USA

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

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

来源：

IMMUNITY | 2013年 / 38卷 / 01期

基金：

比尔及梅琳达.盖茨基金会;

关键词：

NEUTRALIZING ANTIBODIES; MONOCLONAL-ANTIBODIES; V1/V2; DOMAIN; EFFICACY; REACTIVITY; EPITOPES; BINDING; GP41; SOFTWARE; LINEAGE;

D O I：

10.1016/j.immuni.2012.11.011

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The RV144 HIV-1 trial of the canary pox vector (ALVAC-HIV) plus the gp120 AIDSVAX B/E vaccine demonstrated an estimated efficacy of 31%, which correlated directly with antibodies to HIV-1 envelope variable regions 1 and 2 (V1-V2). Genetic analysis of trial viruses revealed increased vaccine efficacy against viruses matching the vaccine strain at V2 residue 169. Here, we isolated four V2 monoclonal antibodies from RV144 vaccinees that recognize residue 169, neutralize laboratory-adapted HIV-1, and mediate killing of field-isolate HIV-1-infected CD4(+) T cells. Crystal structures of two of the V2 antibodies demonstrated that residue 169 can exist within divergent helical and loop conformations, which contrasted dramatically with the 13 strand conformation previously observed with a broadly neutralizing antibody PG9. Thus, RV144 vaccine-induced immune pressure appears to target a region that may be both sequence variable and structurally polymorphic. Variation may signal sites of HIV-1 envelope vulnerability, providing vaccine designers with new options.

引用

页码：176 / 186

页数：11

共 45 条

[1] 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

[2]

Alam S.M., 2012, J VIROL

[3] Human immunodeficiency virus type 1 gp41 antibodies that mask membrane proximal region epitopes: Antibody binding kinetics, induction, and potential for regulation in acute infection [J].

Alam, S. Munir ;

Scearce, Richard M. ;

Parks, Robert J. ;

Plonk, Kelly ;

Plonk, Steven G. ;

Sutherland, Laura L. ;

Gorny, Miroslaw K. ;

Zolla-Pazner, Susan ;

VanLeeuwen, Stacie ;

Moody, M. Anthony ;

Xia, Shi-Mao ;

Montefiori, David C. ;

Tomaras, Georgia D. ;

Weinhold, Kent J. ;

Karim, Salim Abdool ;

Hicks, Charles B. ;

Liao, Hua-Xin ;

Robinson, James ;

Shaw, George M. ;

Haynes, Barton F. .

JOURNAL OF VIROLOGY, 2008, 82 (01) :115-125

[4] 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

[5] Differential Reactivity of Germ Line Allelic Variants of a Broadly Neutralizing HIV-1 Antibody to a gp41 Fusion Intermediate Conformation [J].

Alam, S. Munir ;

Liao, Hua-Xin ;

Dennison, S. Moses ;

Jaeger, Frederick ;

Parks, Robert ;

Anasti, Kara ;

Foulger, Andrew ;

Donathan, Michele ;

Lucas, Judith ;

Verkoczy, Laurent ;

Nicely, Nathan ;

Tomaras, Georgia D. ;

Kelsoe, Garnett ;

Chen, Bing ;

Kepler, Thomas B. ;

Haynes, Barton F. .

JOURNAL OF VIROLOGY, 2011, 85 (22) :11725-11731

[6] 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

[7] Antibody-Dependent Cellular Cytotoxicity-Mediating Antibodies from an HIV-1 Vaccine Efficacy Trial Target Multiple Epitopes and Preferentially Use the VH1 Gene Family [J].

Bonsignori, Mattia ;

Pollara, Justin ;

Moody, M. Anthony ;

Alpert, Michael D. ;

Chen, Xi ;

Hwang, Kwan-Ki ;

Gilbert, Peter B. ;

Huang, Ying ;

Gurley, Thaddeus C. ;

Kozink, Daniel M. ;

Marshall, Dawn J. ;

Whitesides, John F. ;

Tsao, Chun-Yen ;

Kaewkungwal, Jaranit ;

Nitayaphan, Sorachai ;

Pitisuttithum, Punnee ;

Rerks-Ngarm, Supachai ;

Kim, Jerome H. ;

Michael, Nelson L. ;

Tomaras, Georgia D. ;

Montefiori, David C. ;

Lewis, George K. ;

DeVico, Anthony ;

Evans, David T. ;

Ferrari, Guido ;

Liao, Hua-Xin ;

Haynes, Barton F. .

JOURNAL OF VIROLOGY, 2012, 86 (21) :11521-11532

[8] 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

[9] HIV-1 Envelope Induces Memory B Cell Responses That Correlate with Plasma Antibody Levels after Envelope gp120 Protein Vaccination or HIV-1 Infection [J].

Bonsignori, Mattia ;

Moody, M. Anthony ;

Parks, Robert J. ;

Holl, T. Matt ;

Kelsoe, Garnett ;

Hicks, Charles B. ;

Vandergrift, Nathan ;

Tomaras, Georgia D. ;

Haynes, Barton F. .

JOURNAL OF IMMUNOLOGY, 2009, 183 (04) :2708-2717

[10] Neutralizing as well as non-neutralizing polyclonal immunoglobulin (Ig)G from infected patients capture HIV-1 via antibodies directed against the principal immunodominant domain of gp41 [J].

Burrer, R ;

Haessig-Einius, S ;

Aubertin, AM ;

Moog, C .

VIROLOGY, 2005, 333 (01) :102-113

← 1 2 3 4 5 →