Broadly neutralizing antibodies for treatment and prevention of HIV-1 infection

被引:62
作者
Cohen, Yehuda Z. [1 ]
Caskey, Marina [1 ]
机构
[1] Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA
关键词
broadly neutralizing antibodies; clinical trials; HIV cure; HIV reservoir; HUMAN MONOCLONAL-ANTIBODIES; ANTIRETROVIRAL THERAPY; TREATMENT INTERRUPTION; ANTI-HIV-1; ANTIBODIES; HIV-1-INFECTED CELLS; HEALTHY-ADULTS; SHIV INFECTION; IN-VIVO; PROTECTION; MACAQUES;
D O I
10.1097/COH.0000000000000475
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Purpose of reviewSeveral anti-HIV-1 broadly neutralizing antibodies (bNAbs) with exceptional breadth and potency that target different HIV-1 envelope epitopes have been identified. bNAbs are an attractive new strategy for HIV-1 prevention and therapy, and potentially, for long-term remission or cure. Here, we discuss findings from early clinical studies that have evaluated these novel bNAbs.Recent findingsPhase 1 studies of bNAbs targeting two distinct HIV-1 envelope epitopes have demonstrated their favorable safety and pharmacokinetic profile. Single bNAb infusions led to significant, but transient, decline in viremia with selection of escape variants. A single bNAb also delayed viral rebound in ART-treated participants who discontinued ART. Importantly, in-vivo efficacy was related to antibody potency and to the level of preexisting resistance. Studies in animal models showed that bNAbs can clear HIV-infected cells and modulate host immune responses. These findings suggest that bNAbs may target the latent HIV reservoir in humans and could contribute to long-term remission of HIV-1 infection.SummarybNAbs may offer advantages over traditional ART for both the prevention and treatment of HIV-1 infection. In addition, bNAbs may target the latent viral reservoir. bNAb combinations and bNAbs engineered for prolonged half-life and increased potency are currently undergoing clinical evaluation.
引用
收藏
页码:366 / 373
页数:8
相关论文
共 40 条
[1]   Effect of HIV Antibody VRC01 on Viral Rebound after Treatment Interruption [J].
Bar, K. J. ;
Sneller, M. C. ;
Harrison, L. J. ;
Justement, J. S. ;
Overton, E. T. ;
Petrone, M. E. ;
Salantes, D. B. ;
Seamon, C. A. ;
Scheinfeld, B. ;
Kwan, R. W. ;
Learn, G. H. ;
Proschan, M. A. ;
Kreider, E. F. ;
Blazkova, J. ;
Bardsley, M. ;
Refsland, E. W. ;
Messer, M. ;
Clarridge, K. E. ;
Tustin, N. B. ;
Madden, P. J. ;
Oden, K. S. ;
O'Dell, S. J. ;
Jarocki, B. ;
Shiakolas, A. R. ;
Tressler, R. L. ;
Doria-Rose, N. A. ;
Bailer, R. T. ;
Ledgerwood, J. E. ;
Capparelli, E. V. ;
Lynch, R. M. ;
Graham, B. S. ;
Moir, S. ;
Koup, R. A. ;
Mascola, J. R. ;
Hoxie, J. A. ;
Fauci, A. S. ;
Tebas, P. ;
Chun, T-W .
NEW ENGLAND JOURNAL OF MEDICINE, 2016, 375 (21) :2037-2050
[2]   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
[3]   Fcγ receptor pathways during active and passive immunization [J].
Bournazos, Stylianos ;
Ravetch, Jeffrey V. .
IMMUNOLOGICAL REVIEWS, 2015, 268 (01) :88-103
[4]   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
[5]   Elimination of HIV-1-infected cells by broadly neutralizing antibodies [J].
Bruel, Timothee ;
Guivel-Benhassine, Florence ;
Amraoui, Sonia ;
Malbec, Marine ;
Richard, Lea ;
Bourdic, Katia ;
Donahue, Daniel Aaron ;
Lorin, Valerie ;
Casartelli, Nicoletta ;
Noel, Nicolas ;
Lambotte, Olivier ;
Mouquet, Hugo ;
Schwartz, Olivier .
NATURE COMMUNICATIONS, 2016, 7
[6]   Antibody 10-1074 suppresses viremia in HIV-1-infected individuals [J].
Caskey, Marina ;
Schoofs, Till ;
Gruell, Henning ;
Settler, Allison ;
Karagounis, Theodora ;
Kreider, Edward F. ;
Murrell, Ben ;
Pfeifer, Nico ;
Nogueira, Lilian ;
Oliveira, Thiago Y. ;
Learn, Gerald H. ;
Cohen, Yehuda Z. ;
Lehmann, Clara ;
Gillor, Daniel ;
Shimeliovich, Irma ;
Unson-O'Brien, Cecilia ;
Weiland, Daniela ;
Robles, Alexander ;
Kuemmerle, Tim ;
Wyen, Christoph ;
Levin, Rebeka ;
Witmer-Pack, Maggi ;
Eren, Kemal ;
Ignacio, Caroline ;
Kiss, Szilard ;
West, Anthony P., Jr. ;
Mouquet, Hugo ;
Zingman, Barry S. ;
Gulick, Roy M. ;
Keler, Tibor ;
Bjorkman, Pamela J. ;
Seaman, Michael S. ;
Hahn, Beatrice H. ;
Faetkenheuer, Gerd ;
Schlesinger, Sarah J. ;
Nussenzweig, Michel C. ;
Klein, Florian .
NATURE MEDICINE, 2017, 23 (02) :185-191
[7]   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-+
[8]   Neutralizing Activity of Broadly Neutralizing Anti-HIV-1 Antibodies against Clade B Clinical Isolates Produced in Peripheral Blood Mononuclear Cells [J].
Cohen, Yehuda Z. ;
Lorenzi, Julio C. C. ;
Seaman, Michael S. ;
Nogueira, Lilian ;
Schoofs, Till ;
Krassnig, Lisa ;
Butler, Allison ;
Millard, Katrina ;
Fitzsimons, Tomas ;
Daniell, Xiaoju ;
Dizon, Juan P. ;
Shimeliovich, Irina ;
Montefiori, David C. ;
Caskey, Marina ;
Nussenzweig, Michel C. .
JOURNAL OF VIROLOGY, 2018, 92 (05)
[9]   HIV-1 and T cell dynamics after interruption of highly active antiretroviral therapy (HAART) in patients with a history of sustained viral suppression [J].
Davey, RT ;
Bhat, N ;
Yoder, C ;
Chun, TW ;
Metcalf, JA ;
Dewar, R ;
Natarajan, V ;
Lempicki, RA ;
Adelsberger, JW ;
Millers, KD ;
Kovacs, JA ;
Polis, MA ;
Walker, RE ;
Falloon, L ;
Masur, H ;
Gee, D ;
Baseler, M ;
Dimitrov, DS ;
Fauci, AS ;
Lane, HC .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (26) :15109-15114
[10]  
El-Sadr WM, 2006, NEW ENGL J MED, V355, P2283, DOI 10.1056/NEJMoa062360