Cargando…

Increasing the Clinical Potential and Applications of Anti-HIV Antibodies

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Hua, Casey K., Ackerman, Margaret E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5712301/
https://www.ncbi.nlm.nih.gov/pubmed/29234320
http://dx.doi.org/10.3389/fimmu.2017.01655
_version_ 1783283196122628096
author Hua, Casey K.
Ackerman, Margaret E.
author_facet Hua, Casey K.
Ackerman, Margaret E.
author_sort Hua, Casey K.
collection PubMed
description 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.
format Online
Article
Text
id pubmed-5712301
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-57123012017-12-11 Increasing the Clinical Potential and Applications of Anti-HIV Antibodies Hua, Casey K. Ackerman, Margaret E. Front Immunol Immunology 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. Frontiers Media S.A. 2017-11-28 /pmc/articles/PMC5712301/ /pubmed/29234320 http://dx.doi.org/10.3389/fimmu.2017.01655 Text en Copyright © 2017 Hua and Ackerman. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Hua, Casey K.
Ackerman, Margaret E.
Increasing the Clinical Potential and Applications of Anti-HIV Antibodies
title Increasing the Clinical Potential and Applications of Anti-HIV Antibodies
title_full Increasing the Clinical Potential and Applications of Anti-HIV Antibodies
title_fullStr Increasing the Clinical Potential and Applications of Anti-HIV Antibodies
title_full_unstemmed Increasing the Clinical Potential and Applications of Anti-HIV Antibodies
title_short Increasing the Clinical Potential and Applications of Anti-HIV Antibodies
title_sort increasing the clinical potential and applications of anti-hiv antibodies
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5712301/
https://www.ncbi.nlm.nih.gov/pubmed/29234320
http://dx.doi.org/10.3389/fimmu.2017.01655
work_keys_str_mv AT huacaseyk increasingtheclinicalpotentialandapplicationsofantihivantibodies
AT ackermanmargarete increasingtheclinicalpotentialandapplicationsofantihivantibodies