Broadly Neutralizing Antibodies for HIV Eradication

被引:68
作者
Stephenson, Kathryn E. [1 ,2 ]
Barouch, Dan H. [1 ,2 ]
机构
[1] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, E CLS 1043,330 Brookline Ave, Boston, MA 02215 USA
[2] Ragon Inst MGH MIT & Harvard, Boston, MA USA
关键词
HIV; Antibody; Broadly neutralizing antibodies; HIV pathogenesis; Reservoir; bNAb; Eradication; HIV/AIDS; Review; HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN MONOCLONAL-ANTIBODY; PASSIVE IMMUNOTHERAPY; HIV-1-INFECTED HUMANS; PLASMA RICH; ENVELOPE; AIDS; IMMUNIZATION; TRANSFUSIONS; THERAPY;
D O I
10.1007/s11904-016-0299-7
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
Passive transfer of antibodies has long been considered a potential treatment modality for infectious diseases, including HIV. Early efforts to use antibodies to suppress HIV replication, however, were largely unsuccessful, as the antibodies that were studied neutralized only a relatively narrow spectrum of viral strains and were not very potent. Recent advances have led to the discovery of a large portfolio of human monoclonal antibodies that are broadly neutralizing across many HIV-1 subtypes and are also substantially more potent. These antibodies target multiple different epitopes on the HIV envelope, thus allowing for the development of antibody combinations. In this review, we discuss the application of broadly neutralizing antibodies (bNAbs) for HIV treatment and HIV eradication strategies. We highlight bNAbs that target key epitopes, such as the CD4 binding site and the V2/V3-glycan-dependent sites, and we discuss several bNAbs that are currently in the clinical development pipeline.
引用
收藏
页码:31 / 37
页数:7
相关论文
共 50 条
[1]  
[Anonymous], 2014, HIV SURV REP
[2]  
[Anonymous], 2014, GAP REP
[3]   A phase I trial with two human monoclonal antibodies (hMAb 2F5, 2G12) against HIV-1 [J].
Armbruster, C ;
Stiegler, GM ;
Vcelar, BA ;
Jäger, W ;
Michael, NL ;
Vetter, N ;
Katinger, HWD .
AIDS, 2002, 16 (02) :227-233
[4]   Passive immunization with the anti-HIV-1 human monoclonal antibody (hMAb) 4E10 and the hMAb combination 4E10/2F5/2G12 [J].
Armbruster, C ;
Stiegler, GM ;
Vcelar, BA ;
Jäger, W ;
Köller, U ;
Jilch, R ;
Ammann, CG ;
Pruenster, M ;
Stoiber, H ;
Katinger, HWD .
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 2004, 54 (05) :915-920
[5]   Immunologic strategies for HIV-1 remission and eradication [J].
Barouch, Dan H. ;
Deeks, Steven G. .
SCIENCE, 2014, 345 (6193) :169-174
[6]   Therapeutic efficacy of potent neutralizing HIV-1-specific monoclonal antibodies in SHIV-infected rhesus monkeys [J].
Barouch, Dan H. ;
Whitney, James B. ;
Moldt, Brian ;
Klein, Florian ;
Oliveira, Thiago Y. ;
Liu, Jinyan ;
Stephenson, Kathryn E. ;
Chang, Hui-Wen ;
Shekhar, Karthik ;
Gupta, Sanjana ;
Nkolola, Joseph P. ;
Seaman, Michael S. ;
Smith, Kaitlin M. ;
Borducchi, Erica N. ;
Cabral, Crystal ;
Smith, Jeffrey Y. ;
Blackmore, Stephen ;
Sanisetty, Srisowmya ;
Perry, James R. ;
Beck, Matthew ;
Lewis, Mark G. ;
Rinaldi, William ;
Chakraborty, Arup K. ;
Poignard, Pascal ;
Nussenzweig, Michel C. ;
Burton, Dennis R. .
NATURE, 2013, 503 (7475) :224-+
[7]   Broadly Neutralizing Anti-HIV-1 Antibodies Require Fc Effector Functions for In Vivo Activity [J].
Bournazos, Stylianos ;
Klein, Florian ;
Pietzsch, John ;
Seaman, Michael S. ;
Nussenzweig, Michel C. ;
Ravetch, Jeffrey V. .
CELL, 2014, 158 (06) :1243-1253
[8]   Broadly Neutralizing Antibodies Present New Prospects to Counter Highly Antigenically Diverse Viruses [J].
Burton, Dennis R. ;
Poignard, Pascal ;
Stanfield, Robyn L. ;
Wilson, Ian A. .
SCIENCE, 2012, 337 (6091) :183-186
[9]   Viraemia suppressed in HIV-1-infected humans by broadly neutralizing antibody 3BNC117 [J].
Caskey, Marina ;
Klein, Florian ;
Lorenzi, Julio C. C. ;
Seaman, Michael S. ;
West, Anthony P., Jr. ;
Buckley, Noreen ;
Kremer, Gisela ;
Nogueira, Lilian ;
Braunschweig, Malte ;
Scheid, Johannes F. ;
Horwitz, Joshua A. ;
Shimeliovich, Irina ;
Ben-Avraham, Sivan ;
Witmer-Pack, Maggi ;
Platten, Martin ;
Lehmann, Clara ;
Burke, Leah A. ;
Hawthorne, Thomas ;
Gorelick, Robert J. ;
Walker, Bruce D. ;
Keler, Tibor ;
Gulick, Roy M. ;
Faetkenheuer, Gerd ;
Schlesinger, Sarah J. ;
Nussenzweig, Michel C. .
NATURE, 2015, 522 (7557) :487-+
[10]   Broadly neutralizing antibodies suppress HIV in the persistent viral reservoir [J].
Chun, Tae-Wook ;
Murray, Danielle ;
Justement, Jesse S. ;
Blazkova, Jana ;
Hallahan, Claire W. ;
Fankuchen, Olivia ;
Gittens, Kathleen ;
Benko, Erika ;
Kovacs, Colin ;
Moir, Susan ;
Fauci, Anthony S. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2014, 111 (36) :13151-13156