Adeno-associated virus gene therapy–mediated CCR5 blockade suppresses virus replication long term in SHIV-infected macaques
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Le résumé fourni par la source
Adeno-associated virus (AAV) vectors are promising vehicles for the delivery and long-term expression of antibodies for treatment of chronic diseases. Given the strong link between the C-C chemokine receptor 5 (CCR5)–Δ 32/ Δ 32 genotype and protection from HIV, we explored the ability of AAV vectors expressing the CCR5-blocking antibody leronlimab to mediate a functional cure in simian-human immunodeficiency virus (SHIV)–infected rhesus macaques by interrupting viral access to the viral entry co-receptor CCR5. Delivery of AAV-leronlimab to rhesus macaques elicited antidrug antibodies (ADA) and rapid plasma leronlimab clearance in approximately half of the treated macaques. However, in these same animals, we observed spontaneous leronlimab transgene reemergence and detectable CCR5 receptor occupancy approximately 1 year later that subsequently persisted indefinitely without rebound of ADA. In macaques that did not mount robust ADA responses, detectable plasma leronlimab concentrations and CCR5 receptor occupancy were maintained for more than 1 year. Of the nine macaques producing sufficient leronlimab to achieve full CCR5 receptor occupancy on blood CD4 + T cells, AAV-leronlimab drove stringent or partial control of SHIV viremia in six macaques long term. In the three macaques with uncontrolled SHIV viremia, short-term administration of exogenous leronlimab induced complete SHIV suppression in two and a 100-fold reduction in the third, indicating that a threshold of leronlimab expression is necessary to effectively halt SHIV replication. These results demonstrate the potential of gene therapy–mediated long-term antibody-based CCR5 blockade for HIV functional cure but highlight challenges in achieving sufficient antibody expression when targeting an abundant self-antigen.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Adeno-associated virus gene therapy–mediated CCR5 blockade suppresses virus replication long term in SHIV-infected macaques
- Date Crossref
- 29/04/2026
- Éditeur
- American Association for the Advancement of Science (AAAS)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Oregon National Primate Research Center pays non établi dans la noticeStructure de recherche
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University of Miami Department of Pathology pays non établi dans la noticeUniversité ou école supérieure
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Duke University Department of Surgery and Department of Molecular Genetics & pays non établi dans la noticeUniversité ou école supérieure
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University of Massachusetts Chan Medical School Nonhuman Primate Reagent Resource pays non établi dans la noticeUniversité ou école supérieure
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Frederick National Laboratory for Cancer Research AIDS and Cancer Virus Program pays non établi dans la noticeStructure de recherche
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Science University Oregon National Primate Research Center and Vaccine and Gene Therapy Institute pays non établi dans la noticeUniversité ou école supérieure
Oregon National Primate Research Center, Department of Pathology — University of Miami et Department of Surgery and Department of Molecular Genetics & — Duke University, avec 3 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.