Broadly Neutralizing Antibodies as Treatment: Effects on Virus and Immune System

被引:15
作者
Bhiman, Jinal N. [1 ,2 ]
Lynch, Rebecca M. [3 ]
机构
[1] Natl Inst Communicable Dis, Ctr HIV & STIs, Natl Hlth Lab Serv, 1 Modderfontein Rd, ZA-2131 Johannesburg, Gauteng, South Africa
[2] Univ Witwatersrand, Fac Hlth Sci, Johannesburg, South Africa
[3] George Washington Univ, Dept Microbiol Immunol & Trop Med, 2300 Eye St NW, Washington, DC 20001 USA
关键词
Broadly neutralizing antibodies; Passive therapy; Virus escape; HIV-1; monoclonal antibodies; MONOCLONAL-ANTIBODIES; HIV-1; ENVELOPE; HIV-1-INFECTED HUMANS; BISPECIFIC ANTIBODIES; ANTIVIRAL THERAPY; PASSIVE TRANSFER; 2F5; IMMUNOTHERAPY; PREVENTION; INFECTION;
D O I
10.1007/s11904-017-0352-1
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
Purpose of Review The purpose of this study is to summarize recent advances in the use of broadly neutralizing antibodies (bNAbs) as therapeutics in human clinical trials and in non-human primate (NHP) models. We seek to highlight lessons from these studies with an emphasis on consequences to the virus and immune system. Recent Findings In the past 10 years, advances in HIV-1 trimer structure and B cell isolation methods have precipitated the identification of "new-generation" anti-HIV antibodies with broad and potent neutralization. In the past 2 years, the concept of using these bNAbs as therapeutic tools has moved from NHP models into human clinical trials. These trials have investigated the effects of bNAb infusions into patients chronically infected with HIV-1, while the NHP model has investigated treatment during acute infection. Summary Through this work, the relationship between in vitro breadth and potency and in vivo clinical effect, although unresolved, is gradually being elucidated. These results emphasize the need for combination antibody therapy.
引用
收藏
页码:54 / 62
页数:9
相关论文
共 57 条
[1]   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
[2]   Bispecific Antibodies Targeting Different Epitopes on the HIV-1 Envelope Exhibit Broad and Potent Neutralization [J].
Asokan, M. ;
Rudicell, R. S. ;
Louder, M. ;
McKee, K. ;
O'Dell, S. ;
Stewart-Jones, G. ;
Wang, K. ;
Xu, L. ;
Chen, X. ;
Choe, M. ;
Chuang, G. ;
Georgiev, I. S. ;
Joyce, M. G. ;
Kirys, T. ;
Ko, S. ;
Pegu, A. ;
Shi, W. ;
Todd, J. P. ;
Yang, Z. ;
Bailer, R. T. ;
Rao, S. ;
Kwong, P. D. ;
Nabel, G. J. ;
Mascola, J. R. .
JOURNAL OF VIROLOGY, 2015, 89 (24) :12501-12512
[3]   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-+
[4]   Prospects for engineering HIV-specific antibodies for enhanced effector function and half-life [J].
Boesch, Austin W. ;
Alter, Galit ;
Ackerman, Margaret E. .
CURRENT OPINION IN HIV AND AIDS, 2015, 10 (03) :160-169
[5]   Human Immunodeficiency Virus Type 1 Monoclonal Antibodies Suppress Acute Simian-Human Immunodeficiency Virus Viremia and Limit Seeding of Cell-Associated Viral Reservoirs [J].
Bolton, Diane L. ;
Pegu, Amarendra ;
Wang, Keyun ;
McGinnis, Kathleen ;
Nason, Martha ;
Foulds, Kathryn ;
Letukas, Valerie ;
Schmidt, Stephen D. ;
Chen, Xuejun ;
Todd, John Paul ;
Lifson, Jeffrey D. ;
Rao, Srinivas ;
Michael, Nelson L. ;
Robb, Merlin L. ;
Mascola, John R. ;
Koup, Richard A. .
JOURNAL OF VIROLOGY, 2016, 90 (03) :1321-1332
[6]   Bispecific Anti-HIV-1 Antibodies with Enhanced Breadth and Potency [J].
Bournazos, Stylianos ;
Gazumyan, Anna ;
Seaman, Michael S. ;
Nussenzweig, Michel C. ;
Ravetch, Jeffrey V. .
CELL, 2016, 165 (07) :1609-1620
[7]  
Bruel TEE, 2016, NATURE COMMUNICATION, V6, P1
[8]   Antibody responses to envelope glycoproteins in HIV-1 infection [J].
Burton, Dennis R. ;
Mascola, John R. .
NATURE IMMUNOLOGY, 2015, 16 (06) :571-576
[9]   Sustained virologic control in SIV+ macaques after antiretroviral and α4β7 antibody therapy (Publication with Expression of Concern. See vol. 365, pg. 991, 2019) [J].
Byrareddy, Siddappa N. ;
Arthos, James ;
Cicala, Claudia ;
Villinger, Francois ;
Ortiz, Kristina T. ;
Little, Dawn ;
Sidell, Neil ;
Kane, Maureen A. ;
Yu, Jianshi ;
Jones, Jace W. ;
Santangelo, Philip J. ;
Zurla, Chiara ;
McKinnon, Lyle R. ;
Arnold, Kelly B. ;
Woody, Caroline E. ;
Walter, Lutz ;
Roos, Christian ;
Noll, Angela ;
Van Ryk, Donald ;
Jelicic, Katija ;
Cimbro, Raffaello ;
Gumber, Sanjeev ;
Reid, Michelle D. ;
Adsay, Volkan ;
Amancha, Praveen K. ;
Mayne, Ann E. ;
Parslow, Tristram G. ;
Fauci, Anthony S. ;
Ansari, Aftab A. .
SCIENCE, 2016, 354 (6309) :197-202
[10]   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-+