HIV Antibodies for Treatment of HIV Infection

Overview

Journal Immunol Rev

Specialties Allergy & Immunology
General Surgery

Date 2017 Jan 31

PMID 28133794

Citations 45

Authors

David M Margolis

Richard A Koup

Guido Ferrari

Affiliations

Soon will be listed here.

Abstract

The bar is high to improve on current combination antiretroviral therapy (ART), now highly effective, safe, and simple. However, antibodies that bind the HIV envelope are able to uniquely target the virus as it seeks to enter new target cells, or as it is expressed from previously infected cells. Furthermore, the use of antibodies against HIV as a therapeutic may offer advantages. Antibodies can have long half-lives, and are being considered as partners for long-acting antiretrovirals for use in therapy or prevention of HIV infection. Early studies in animal models and in clinical trials suggest that such antibodies can have antiviral activity but, as with small-molecule antiretrovirals, the issues of viral escape and resistance will have to be addressed. Most promising, however, are the unique properties of anti-HIV antibodies: the potential ability to opsonize viral particles, to direct antibody-dependent cellular cytotoxicity (ADCC) against actively infected cells, and ultimately the ability to direct the clearance of HIV-infected cells by effector cells of the immune system. These distinctive activities suggest that HIV antibodies and their derivatives may play an important role in the next frontier of HIV therapeutics, the effort to develop treatments that could lead to an HIV cure.

Citing Articles

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References

Diskin R, Scheid J, Marcovecchio P, West Jr A, Klein F, Gao H . Increasing the potency and breadth of an HIV antibody by using structure-based rational design. Science. 2011; 334(6060):1289-93. PMC: 3232316. DOI: 10.1126/science.1213782. View

Chomont N, El-Far M, Ancuta P, Trautmann L, Procopio F, Yassine-Diab B . HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation. Nat Med. 2009; 15(8):893-900. PMC: 2859814. DOI: 10.1038/nm.1972. View

Chung A, Ghebremichael M, Robinson H, Brown E, Choi I, Lane S . Polyfunctional Fc-effector profiles mediated by IgG subclass selection distinguish RV144 and VAX003 vaccines. Sci Transl Med. 2014; 6(228):228ra38. DOI: 10.1126/scitranslmed.3007736. View

Yates N, Liao H, Fong Y, deCamp A, Vandergrift N, Williams W . Vaccine-induced Env V1-V2 IgG3 correlates with lower HIV-1 infection risk and declines soon after vaccination. Sci Transl Med. 2014; 6(228):228ra39. PMC: 4116665. DOI: 10.1126/scitranslmed.3007730. View

Llibre J, Buzon M, Massanella M, Esteve A, Dahl V, Puertas M . Treatment intensification with raltegravir in subjects with sustained HIV-1 viraemia suppression: a randomized 48-week study. Antivir Ther. 2012; 17(2):355-64. DOI: 10.3851/IMP1917. View

Mabondzo A, Aussage P, Bartholeyns J, Le Naour R, Raoul H, Dormont D . Bispecific antibody targeting of human immunodeficiency virus type 1 (HIV-1) glycoprotein 41 to human macrophages through the Fc IgG receptor I mediates neutralizing effects in HIV-1 infection. J Infect Dis. 1992; 166(1):93-9. DOI: 10.1093/infdis/166.1.93. View

Pincus S, Wehrly K, Cole R, Fang H, LEWIS G, McClure J . In vitro effects of anti-HIV immunotoxins directed against multiple epitopes on HIV type 1 envelope glycoprotein 160. AIDS Res Hum Retroviruses. 1996; 12(11):1041-51. DOI: 10.1089/aid.1996.12.1041. View

Fuchs S, Martinez-Navio J, Piatak Jr M, Lifson J, Gao G, Desrosiers R . AAV-Delivered Antibody Mediates Significant Protective Effects against SIVmac239 Challenge in the Absence of Neutralizing Activity. PLoS Pathog. 2015; 11(8):e1005090. PMC: 4527674. DOI: 10.1371/journal.ppat.1005090. View

Perrin L, Zinkernagel R, Oldstone M . Immune response in humans after vaccination with vaccinia virus: generation of a virus-specific cytotoxic activity by human peripheral lymphocytes. J Exp Med. 1977; 146(4):949-69. PMC: 2180809. DOI: 10.1084/jem.146.4.949. View

10.

Bonsignori M, Pollara J, Moody M, Alpert M, Chen X, Hwang K . Antibody-dependent cellular cytotoxicity-mediating antibodies from an HIV-1 vaccine efficacy trial target multiple epitopes and preferentially use the VH1 gene family. J Virol. 2012; 86(21):11521-32. PMC: 3486290. DOI: 10.1128/JVI.01023-12. View

11.

Poignard P, Sabbe R, Picchio G, Wang M, Gulizia R, Katinger H . Neutralizing antibodies have limited effects on the control of established HIV-1 infection in vivo. Immunity. 1999; 10(4):431-8. DOI: 10.1016/s1074-7613(00)80043-6. View

12.

Barouch D, Whitney J, Moldt B, Klein F, Oliveira T, Liu J . Therapeutic efficacy of potent neutralizing HIV-1-specific monoclonal antibodies in SHIV-infected rhesus monkeys. Nature. 2013; 503(7475):224-8. PMC: 4017780. DOI: 10.1038/nature12744. View

13.

Wei X, Decker J, Wang S, Hui H, Kappes J, Wu X . Antibody neutralization and escape by HIV-1. Nature. 2003; 422(6929):307-12. DOI: 10.1038/nature01470. View

14.

Buzon M, Massanella M, Llibre J, Esteve A, Dahl V, Puertas M . HIV-1 replication and immune dynamics are affected by raltegravir intensification of HAART-suppressed subjects. Nat Med. 2010; 16(4):460-5. DOI: 10.1038/nm.2111. View

15.

Wyatt R, Moore J, Accola M, Desjardin E, Robinson J, Sodroski J . Involvement of the V1/V2 variable loop structure in the exposure of human immunodeficiency virus type 1 gp120 epitopes induced by receptor binding. J Virol. 1995; 69(9):5723-33. PMC: 189432. DOI: 10.1128/JVI.69.9.5723-5733.1995. View

16.

Chan D, Kim P . HIV entry and its inhibition. Cell. 1998; 93(5):681-4. DOI: 10.1016/s0092-8674(00)81430-0. View

17.

Sattentau Q . Avoiding the void: cell-to-cell spread of human viruses. Nat Rev Microbiol. 2008; 6(11):815-26. DOI: 10.1038/nrmicro1972. View

18.

Sloan D, Lam C, Irrinki A, Liu L, Tsai A, Pace C . Targeting HIV Reservoir in Infected CD4 T Cells by Dual-Affinity Re-targeting Molecules (DARTs) that Bind HIV Envelope and Recruit Cytotoxic T Cells. PLoS Pathog. 2015; 11(11):e1005233. PMC: 4634948. DOI: 10.1371/journal.ppat.1005233. View

19.

Stoddart C, Galkina S, Joshi P, Kosikova G, Long B, Maidji E . Efficacy of broadly neutralizing monoclonal antibody PG16 in HIV-infected humanized mice. Virology. 2014; 462-463:115-25. PMC: 4125441. DOI: 10.1016/j.virol.2014.05.036. View

20.

Bird R, Walker B . Single chain antibody variable regions. Trends Biotechnol. 1991; 9(4):132-7. DOI: 10.1016/0167-7799(91)90044-i. View