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      Antibody-Mediated Therapy against HIV/AIDS: Where Are We Standing Now?

      review-article
      ,
      Journal of Pathogens
      Hindawi

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          Abstract

          Acquired immunodeficiency syndrome (AIDS) cases are on the rise globally. To date, there is still no effective measure to eradicate the causative agent, human immunodeficiency virus (HIV). Highly active antiretroviral therapy (HAART) is being used in HIV/AIDS management, but it results in long-term medication and has major drawbacks such as multiple side effects, high cost, and increasing the generation rate of escape mutants. In addition, HAART does not control HIV-related complications, and hence more medications and further management are required. With this, other alternatives are urgently needed. In the past, small-molecule inhibitors have shown potent antiviral effects, and some of them are now being evaluated in clinical trials. The challenges in developing these small molecules for clinical use include the off-target effect, poor stability, and low bioavailability. On the other hand, antibody-mediated therapy has emerged as an important therapeutic modality for anti-HIV therapeutics development. Many antiviral antibodies, namely, broad neutralizing antibodies (bnAbs) against multiple strains of HIV, have shown promising effects in vitro and in animal studies; further studies are ongoing in clinical trials to evaluate their uses in clinical applications. This short review aims to discuss the current development of therapeutic antibodies against HIV and the challenges in adopting them for clinical use.

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          Most cited references72

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          Broadly Neutralizing Antibodies to HIV and Their Role in Vaccine Design.

          HIV employs multiple means to evade the humoral immune response, particularly the elicitation of and recognition by broadly neutralizing antibodies (bnAbs). Such antibodies can act antivirally against a wide spectrum of viruses by targeting relatively conserved regions on the surface HIV envelope trimer spike. Elicitation of and recognition by bnAbs are hindered by the arrangement of spikes on virions and the relatively difficult access to bnAb epitopes on spikes, including the proximity of variable regions and a high density of glycans. Yet, in a small proportion of HIV-infected individuals, potent bnAb responses do develop, and isolation of the corresponding monoclonal antibodies has been facilitated by identification of favorable donors with potent bnAb sera and by development of improved methods for human antibody generation. Molecular studies of recombinant Env trimers, alone and in interaction with bnAbs, are providing new insights that are fueling the development and testing of promising immunogens aimed at the elicitation of bnAbs.
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            Broadly neutralizing anti-HIV-1 antibodies require Fc effector functions for in vivo activity.

            Broadly neutralizing antibodies (bNAbs) against HIV-1 provide both effective pre-exposure prophylaxis and treatment of HIV-1 infection in murine and nonhuman primate models, suggesting their potential use in humans. Although much is known about the role of variable domains in the neutralization breadth and potency of these bNAbs, the contribution of Fc domains to their activities is, by contrast, poorly characterized. Assessment of the in vivo activity of several bNAbs revealed that FcγR-mediated effector function contributes substantially to their capacity to block viral entry, suppress viremia, and confer therapeutic activity. Enhanced in vivo potency of anti-HIV-1 bNAbs was associated with preferential engagement of activating, but not inhibitory FcγRs, and Fc domain-engineered bNAb variants with selective binding capacity for activating FcγRs displayed augmented protective activity. These findings reveal key roles for Fc effector function in the in vivo activity of anti-HIV-1 bNAbs and provide strategies for generating bNAbs with improved efficacy. Copyright © 2014 Elsevier Inc. All rights reserved.
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              Long-acting intramuscular cabotegravir and rilpivirine in adults with HIV-1 infection (LATTE-2): 96-week results of a randomised, open-label, phase 2b, non-inferiority trial

              Cabotegravir and rilpivirine are antiretroviral drugs in development as long-acting injectable formulations. The LATTE-2 study evaluated long-acting cabotegravir plus rilpivirine for maintenance of HIV-1 viral suppression through 96 weeks.
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                Author and article information

                Contributors
                Journal
                J Pathog
                J Pathog
                JPATH
                Journal of Pathogens
                Hindawi
                2090-3057
                2090-3065
                2018
                3 June 2018
                : 2018
                : 8724549
                Affiliations
                Department of Medical Sciences (DMS), School of Healthcare and Medical Sciences (SHMS), Sunway University, Jalan Universiti, Bandar Sunway, 47500 Subang Jaya, Selangor Darul Ehsan, Malaysia
                Author notes

                Academic Editor: Nongnuch Vanittanakom

                Author information
                http://orcid.org/0000-0002-3824-0224
                Article
                10.1155/2018/8724549
                6009031
                29973995
                01509294-a4ba-43c5-a04a-57f3d106d3a0
                Copyright © 2018 Noel Jacques Awi and Sin-Yeang Teow.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 25 January 2018
                : 10 April 2018
                : 26 April 2018
                Funding
                Funded by: Sunway University
                Award ID: INT-2018-SHMS-SIHD-01
                Funded by: Majlis Kanser Nasional
                Award ID: EXT-SIDS-SIHD-MAKNA-2017-01
                Categories
                Review Article

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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