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Promise and problems associated with the use of recombinant AAV for the delivery of anti-HIV antibodies
Attempts to elicit antibodies with potent neutralizing activity against a broad range of human immunodeficiency virus (HIV) isolates have so far proven unsuccessful. Long-term delivery of monoclonal antibodies (mAbs) with such activity is a creative alternative that circumvents the need for an immun...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5289440/ https://www.ncbi.nlm.nih.gov/pubmed/28197421 http://dx.doi.org/10.1038/mtm.2016.68 |
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author | Fuchs, Sebastian P Desrosiers, Ronald C |
author_facet | Fuchs, Sebastian P Desrosiers, Ronald C |
author_sort | Fuchs, Sebastian P |
collection | PubMed |
description | Attempts to elicit antibodies with potent neutralizing activity against a broad range of human immunodeficiency virus (HIV) isolates have so far proven unsuccessful. Long-term delivery of monoclonal antibodies (mAbs) with such activity is a creative alternative that circumvents the need for an immune response and has the potential for creating a long-lasting sterilizing barrier against HIV. This approach is made possible by an incredible array of potent broadly neutralizing antibodies (bnAbs) that have been identified over the last several years. Recombinant adeno-associated virus (rAAV) vectors are ideally suited for long-term delivery for a variety of reasons. The only products made from rAAV are derived from the transgenes that are put into it; as long as those products are not viewed as foreign, expression from muscle tissue may continue for decades. Thus, use of rAAV to achieve long-term delivery of anti-HIV mAbs with potent neutralizing activity against a broad range of HIV-1 isolates is emerging as a promising concept for the prevention or treatment of HIV-1 infection in humans. Experiments in mice and monkeys that have demonstrated protective efficacy against AIDS virus infection have raised hopes for the promise of this approach. However, all published experiments in monkeys have encountered unwanted immune responses to the AAV-delivered antibody, and these immune responses appear to limit the levels of delivered antibody that can be achieved. In this review, we highlight the promise of rAAV-mediated antibody delivery for the prevention or treatment of HIV infection in humans, but we also discuss the obstacles that will need to be understood and solved in order for the promise of this approach to be realized. |
format | Online Article Text |
id | pubmed-5289440 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-52894402017-02-14 Promise and problems associated with the use of recombinant AAV for the delivery of anti-HIV antibodies Fuchs, Sebastian P Desrosiers, Ronald C Mol Ther Methods Clin Dev Review Article Attempts to elicit antibodies with potent neutralizing activity against a broad range of human immunodeficiency virus (HIV) isolates have so far proven unsuccessful. Long-term delivery of monoclonal antibodies (mAbs) with such activity is a creative alternative that circumvents the need for an immune response and has the potential for creating a long-lasting sterilizing barrier against HIV. This approach is made possible by an incredible array of potent broadly neutralizing antibodies (bnAbs) that have been identified over the last several years. Recombinant adeno-associated virus (rAAV) vectors are ideally suited for long-term delivery for a variety of reasons. The only products made from rAAV are derived from the transgenes that are put into it; as long as those products are not viewed as foreign, expression from muscle tissue may continue for decades. Thus, use of rAAV to achieve long-term delivery of anti-HIV mAbs with potent neutralizing activity against a broad range of HIV-1 isolates is emerging as a promising concept for the prevention or treatment of HIV-1 infection in humans. Experiments in mice and monkeys that have demonstrated protective efficacy against AIDS virus infection have raised hopes for the promise of this approach. However, all published experiments in monkeys have encountered unwanted immune responses to the AAV-delivered antibody, and these immune responses appear to limit the levels of delivered antibody that can be achieved. In this review, we highlight the promise of rAAV-mediated antibody delivery for the prevention or treatment of HIV infection in humans, but we also discuss the obstacles that will need to be understood and solved in order for the promise of this approach to be realized. Nature Publishing Group 2016-11-16 /pmc/articles/PMC5289440/ /pubmed/28197421 http://dx.doi.org/10.1038/mtm.2016.68 Text en Copyright © 2016 Official journal of the American Society of Gene & Cell Therapy http://creativecommons.org/licenses/by-nc-sa/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/ |
spellingShingle | Review Article Fuchs, Sebastian P Desrosiers, Ronald C Promise and problems associated with the use of recombinant AAV for the delivery of anti-HIV antibodies |
title | Promise and problems associated with the use of recombinant AAV for the delivery of anti-HIV antibodies |
title_full | Promise and problems associated with the use of recombinant AAV for the delivery of anti-HIV antibodies |
title_fullStr | Promise and problems associated with the use of recombinant AAV for the delivery of anti-HIV antibodies |
title_full_unstemmed | Promise and problems associated with the use of recombinant AAV for the delivery of anti-HIV antibodies |
title_short | Promise and problems associated with the use of recombinant AAV for the delivery of anti-HIV antibodies |
title_sort | promise and problems associated with the use of recombinant aav for the delivery of anti-hiv antibodies |
topic | Review Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5289440/ https://www.ncbi.nlm.nih.gov/pubmed/28197421 http://dx.doi.org/10.1038/mtm.2016.68 |
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