Adeno-associated virus-vectored delivery of HIV biologics: the promise of a “single-shot” functional cure for HIV infection
The ability of immunoglobulin-based HIV biologics (Ig-HIV), including broadly neutralizing antibodies, to suppress viral replication in pre-clinical and clinical studies illustrates how these molecules can serve as alternatives or adjuncts to antiretroviral therapy for treating HIV infection. Howeve...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-03-01
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| Series: | Journal of Virus Eradication |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S205566402300002X |
| _version_ | 1827962604134334464 |
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| author | Patricia A. Hahn Mauricio A. Martins |
| author_facet | Patricia A. Hahn Mauricio A. Martins |
| author_sort | Patricia A. Hahn |
| collection | DOAJ |
| description | The ability of immunoglobulin-based HIV biologics (Ig-HIV), including broadly neutralizing antibodies, to suppress viral replication in pre-clinical and clinical studies illustrates how these molecules can serve as alternatives or adjuncts to antiretroviral therapy for treating HIV infection. However, the current paradigm for delivering Ig-HIVs requires repeated passive infusions, which faces both logistical and economic challenges to broad-scale implementation. One promising way to overcome these obstacles and achieve sustained expression of Ig-HIVs in vivo involves the transfer of Ig-HIV genes to host cells utilizing adeno-associated virus (AAV) vectors. Because AAV vectors are non-pathogenic and their genomes persist in the cell nucleus as episomes, transgene expression can last for as long as the AAV-transduced cell lives. Given the long lifespan of myocytes, skeletal muscle is a preferred tissue for AAV-based immunotherapies aimed at achieving persistent delivery of Ig-HIVs. Consistent with this idea, recent studies suggest that lifelong immunity against HIV can be achieved from a one-time intramuscular dose of AAV/Ig-HIV vectors. However, realizing the promise of this approach faces significant hurdles, including the potential of AAV-delivered Ig-HIVs to induce anti-drug antibodies and the high AAV seroprevalence in the human population. Here we describe how these host immune responses can hinder AAV/Ig-HIV therapies and review current strategies for overcoming these barriers. Given the potential of AAV/Ig-HIV therapy to maintain ART-free virologic suppression and prevent HIV reinfection in people living with HIV, optimizing this strategy should become a greater priority in HIV/AIDS research. |
| first_indexed | 2024-04-09T16:45:02Z |
| format | Article |
| id | doaj.art-b257cbcb4e9845d39f8567177553cf5d |
| institution | Directory Open Access Journal |
| issn | 2055-6640 |
| language | English |
| last_indexed | 2024-04-09T16:45:02Z |
| publishDate | 2023-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Virus Eradication |
| spelling | doaj.art-b257cbcb4e9845d39f8567177553cf5d2023-04-23T06:06:01ZengElsevierJournal of Virus Eradication2055-66402023-03-0191100316Adeno-associated virus-vectored delivery of HIV biologics: the promise of a “single-shot” functional cure for HIV infectionPatricia A. Hahn0Mauricio A. Martins1Department of Immunology and Microbiology, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, FL, 33458, USA; The Skaggs Graduate School, The Scripps Research Institute, Jupiter, FL, 33458, USADepartment of Immunology and Microbiology, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, FL, 33458, USA; Corresponding author.The ability of immunoglobulin-based HIV biologics (Ig-HIV), including broadly neutralizing antibodies, to suppress viral replication in pre-clinical and clinical studies illustrates how these molecules can serve as alternatives or adjuncts to antiretroviral therapy for treating HIV infection. However, the current paradigm for delivering Ig-HIVs requires repeated passive infusions, which faces both logistical and economic challenges to broad-scale implementation. One promising way to overcome these obstacles and achieve sustained expression of Ig-HIVs in vivo involves the transfer of Ig-HIV genes to host cells utilizing adeno-associated virus (AAV) vectors. Because AAV vectors are non-pathogenic and their genomes persist in the cell nucleus as episomes, transgene expression can last for as long as the AAV-transduced cell lives. Given the long lifespan of myocytes, skeletal muscle is a preferred tissue for AAV-based immunotherapies aimed at achieving persistent delivery of Ig-HIVs. Consistent with this idea, recent studies suggest that lifelong immunity against HIV can be achieved from a one-time intramuscular dose of AAV/Ig-HIV vectors. However, realizing the promise of this approach faces significant hurdles, including the potential of AAV-delivered Ig-HIVs to induce anti-drug antibodies and the high AAV seroprevalence in the human population. Here we describe how these host immune responses can hinder AAV/Ig-HIV therapies and review current strategies for overcoming these barriers. Given the potential of AAV/Ig-HIV therapy to maintain ART-free virologic suppression and prevent HIV reinfection in people living with HIV, optimizing this strategy should become a greater priority in HIV/AIDS research.http://www.sciencedirect.com/science/article/pii/S205566402300002X |
| spellingShingle | Patricia A. Hahn Mauricio A. Martins Adeno-associated virus-vectored delivery of HIV biologics: the promise of a “single-shot” functional cure for HIV infection Journal of Virus Eradication |
| title | Adeno-associated virus-vectored delivery of HIV biologics: the promise of a “single-shot” functional cure for HIV infection |
| title_full | Adeno-associated virus-vectored delivery of HIV biologics: the promise of a “single-shot” functional cure for HIV infection |
| title_fullStr | Adeno-associated virus-vectored delivery of HIV biologics: the promise of a “single-shot” functional cure for HIV infection |
| title_full_unstemmed | Adeno-associated virus-vectored delivery of HIV biologics: the promise of a “single-shot” functional cure for HIV infection |
| title_short | Adeno-associated virus-vectored delivery of HIV biologics: the promise of a “single-shot” functional cure for HIV infection |
| title_sort | adeno associated virus vectored delivery of hiv biologics the promise of a single shot functional cure for hiv infection |
| url | http://www.sciencedirect.com/science/article/pii/S205566402300002X |
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