Engineering broadly neutralizing antibodies for HIV prevention and therapy

被引:16
作者
Hua, Casey K. [1 ]
Ackerman, Margaret E. [1 ,2 ]
机构
[1] Geisel Sch Med, Dept Microbiol & Immunol, Lebanon, NH USA
[2] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA
关键词
Antibody; Therapy; Prevention; HIV; Effector function; Neutralization; HUMAN-IMMUNODEFICIENCY-VIRUS; DEPENDENT CELLULAR CYTOTOXICITY; NEONATAL FC-RECEPTOR; HUMAN MONOCLONAL-ANTIBODIES; HIV-1/SIV CHIMERIC VIRUS; MUCOSAL SHIV CHALLENGE; T-LYMPHOCYTE RESPONSES; MEDIATED GENE-TRANSFER; PBL-SCID MICE; IN-VITRO;
D O I
10.1016/j.addr.2016.01.013
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
A combination of advances spanning from isolation to delivery of potent HIV-specific antibodies has begun to revolutionize understandings of antibody-mediated antiviral activity. As a result, the set of broadly neutralizing and highly protective antibodies has grown in number, diversity, potency, and breadth of viral recognition and neutralization. These antibodies are now being further enhanced by rational engineering of their anti-HIV activities and coupled to cutting edge gene delivery and strategies to optimize their pharmacokinetics and biodistribution. As a result, the prospects for clinical use of HIV-specific antibodies to treat, clear, and prevent HIV infection are gaining momentum. Here we discuss the diverse methods whereby antibodies are being optimized for neutralization potency and breadth, biodistribution, pharmacokinetics, and effector function with the aim of revolutionizing HIV treatment and prevention options. (C) 2016 Elsevier B.V. All rights reserved.
引用
收藏
页码:157 / 173
页数:17
相关论文
共 332 条
[1]   Detection of antibody-dependent complement-mediated inactivation of both autologous and heterologous virus in primary human immunodeficiency virus type I infection [J].
Aasa-Chapman, MMI ;
Holuigue, S ;
Aubin, K ;
Wong, M ;
Jones, NA ;
Cornforth, D ;
Pellegrino, P ;
Newton, P ;
Williams, I ;
Borrow, P ;
Mcknight, A .
JOURNAL OF VIROLOGY, 2005, 79 (05) :2823-2830
[2]   Polyfunctional HIV-Specific Antibody Responses Are Associated with Spontaneous HIV Control [J].
Ackerman, Margaret E. ;
Mikhailova, Anastassia ;
Brown, Eric P. ;
Dowell, Karen G. ;
Walker, Bruce D. ;
Bailey-Kellogg, Chris ;
Suscovich, Todd J. ;
Alter, Galit .
PLOS PATHOGENS, 2016, 12 (01)
[3]   Natural variation in Fc glycosylation of HIV-specific antibodies impacts antiviral activity [J].
Ackerman, Margaret E. ;
Crispin, Max ;
Yu, Xiaojie ;
Baruah, Kavitha ;
Boesch, Austin W. ;
Harvey, David J. ;
Dugast, Anne-Sophie ;
Heizen, Erin L. ;
Ercan, Altan ;
Choi, Ickwon ;
Streeck, Hendrik ;
Nigrovic, Peter A. ;
Bailey-Kellogg, Chris ;
Scanlan, Chris ;
Alter, Galit .
JOURNAL OF CLINICAL INVESTIGATION, 2013, 123 (05) :2183-2192
[4]   Enhanced Phagocytic Activity of HIV-Specific Antibodies Correlates with Natural Production of Immunoglobulins with Skewed Affinity for FcγR2a and FcγR2b [J].
Ackerman, Margaret E. ;
Dugast, Anne-Sophie ;
McAndrew, Elizabeth G. ;
Tsoukas, Stephen ;
Licht, Anna F. ;
Irvine, Darrell J. ;
Alter, Galit .
JOURNAL OF VIROLOGY, 2013, 87 (10) :5468-5476
[5]   Emerging Concepts on the Role of Innate Immunity in the Prevention and Control of HIV Infection [J].
Ackerman, Margaret E. ;
Dugast, Anne-Sophie ;
Alter, Galit .
ANNUAL REVIEW OF MEDICINE, VOL 63, 2012, 63 :113-130
[6]   Evidence for a correlation between antibody-dependent cellular cytotoxicity-mediating Anti-HIV-1 antibodies and prognostic predictors of HIV infection [J].
Ahmad, R ;
Sindhu, STAK ;
Toma, E ;
Morisset, R ;
Vincelette, J ;
Menezes, J ;
Ahmad, A .
JOURNAL OF CLINICAL IMMUNOLOGY, 2001, 21 (03) :227-233
[7]   A Novel Role for the IgG Fc Glycan: The Anti-inflammatory Activity of Sialylated IgG Fcs [J].
Anthony, Robert M. ;
Ravetch, Jeffrey V. .
JOURNAL OF CLINICAL IMMUNOLOGY, 2010, 30 :S9-S14
[8]  
Asokan M., 2015, J VIROL
[9]   Human neutralizing monoclonal antibodies of the IgG1 subtype protect against mucosal simian-human immunodeficiency virus infection [J].
Baba, TW ;
Liska, V ;
Hofmann-Lehmann, R ;
Vlasak, J ;
Xu, WD ;
Ayehunie, S ;
Cavacini, LA ;
Posner, MR ;
Katinger, H ;
Stiegler, G ;
Bernacky, BJ ;
Rizvi, TA ;
Schmidt, R ;
Hill, LR ;
Keeling, ME ;
Lu, YC ;
Wright, JE ;
Chou, TC ;
Ruprecht, RM .
NATURE MEDICINE, 2000, 6 (02) :200-206
[10]   Vectored immunoprophylaxis protects humanized mice from mucosal HIV transmission [J].
Balazs, Alejandro B. ;
Ouyang, Yong ;
Hong, Christin M. ;
Chen, Joyce ;
Nguyen, Steven M. ;
Rao, Dinesh S. ;
An, Dong Sung ;
Baltimore, David .
NATURE MEDICINE, 2014, 20 (03) :296-300