Increasing the Clinical Potential and Applications of Anti-HIV Antibodies

Abstract

Preclinical and early human clinical studies of broadly neutralizing antibodies (bNAbs) to prevent and treat HIV infection support the clinical utility and potential of bNAbs for prevention, postexposure prophylaxis, and treatment of acute and chronic infection. Observed and potential limitations of bNAbs from these recent studies include the selection of resistant viral populations, immunogenicity resulting in the development of antidrug (Ab) responses, and the potentially toxic elimination of reservoir cells in regeneration-limited tissues. Here, we review opportunities to improve the clinical utility of HIV Abs to address these challenges and further accomplish functional targets for anti-HIV Ab therapy at various stages of exposure/infection. Before exposure, bNAbs’ ability to serve as prophylaxis by neutralization may be improved by increasing serum half-life to necessitate less frequent administration, delivering genes for durable in vivo expression, and targeting bNAbs to sites of exposure. After exposure and/or in the setting of acute infection, bNAb use to prevent/reduce viral reservoir establishment and spread may be enhanced by increasing the potency with which autologous adaptive immune responses are stimulated, clearing acutely infected cells, and preventing cell–cell transmission of virus. In the setting of chronic infection, bNAbs may better mediate viral remission or “cure” in combination with antiretroviral therapy and/or latency reversing agents, by targeting additional markers of tissue reservoirs or infected cell types, or by serving as targeting moieties in engineered cell therapy. While the clinical use of HIV Abs has never been closer, remaining studies to precisely define, model, and understand the complex roles and dynamics of HIV Abs and viral evolution in the context of the human immune system and anatomical compartmentalization will be critical to both optimize their clinical use in combination with existing agents and define further strategies with which to enhance their clinical safety and efficacy.

Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults

“…152–154 Newer approaches to increase the potency, breadth, 155 and half-life 156,157 of bNAbs, evaluate different methods of bNAb administration, 158 and assess the efficacy of combinations of bNAbs are being investigated. 159,160 …”

Update on Fc-Mediated Antibody Functions Against HIV-1 Beyond Neutralization

“…During the last decade, a whole new series of broadly neutralizing Abs (bNAbs), which are NAbs with exceptional potency and breadth, have been isolated (4)(5)(6) and have efficiently protected humanized mice and non-human primates (NHPs) from experimental challenge. Some of these bNAbs are undergoing testing in human clinical prevention and therapeutic trials (6)(7)(8)(9)(10)(11)(12)(13)(14). FIGURE 1 | Distinct inhibitory activities of Abs in HIV target cells.…”

Letter to the Editor: Issues on COVID-19 Pathogenesis

“…Antibody-dependent enhancement (ADE) resulting from successive infections by antigenically related viruses has been extensively described and recognized as an important mechanism of viral pathogenesis. In vitro and/or in vivo evidence of ADE has been reported for several viruses, such as human immunodeficiency (11), influenza (28), Ebola (18) and dengue (DENV) viruses (10).…”