دورية أكاديمية
Suppression of human and simian immunodeficiency virus replication with the CCR5-specific antibody Leronlimab in two species.
| العنوان: | Suppression of human and simian immunodeficiency virus replication with the CCR5-specific antibody Leronlimab in two species. |
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| المؤلفون: | Xiao L Chang, Jason S Reed, Gabriela M Webb, Helen L Wu, Jimmy Le, Katherine B Bateman, Justin M Greene, Cleiton Pessoa, Courtney Waytashek, Whitney C Weber, Joseph Hwang, Miranda Fischer, Cassandra Moats, Oriene Shiel, Rachele M Bochart, Hugh Crank, Don Siess, Travis Giobbi, Jeffrey Torgerson, Rebecca Agnor, Lina Gao, Kush Dhody, Jacob P Lalezari, Ivo Sah Bandar, Alnor M Carnate, Alina S Pang, Michael J Corley, Scott Kelly, Nader Pourhassan, Jeremy Smedley, Benjamin N Bimber, Scott G Hansen, Lishomwa C Ndhlovu, Jonah B Sacha |
| المصدر: | PLoS Pathogens, Vol 18, Iss 3, p e1010396 (2022) |
| بيانات النشر: | Public Library of Science (PLoS), 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Immunologic diseases. Allergy LCC:Biology (General) |
| مصطلحات موضوعية: | Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5 |
| الوصف: | The CCR5-specific antibody Leronlimab is being investigated as a novel immunotherapy that can suppress HIV replication with minimal side effects. Here we studied the virological and immunological consequences of Leronlimab in chronically CCR5-tropic HIV-1 infected humans (n = 5) on suppressive antiretroviral therapy (ART) and in ART-naïve acutely CCR5-tropic SHIV infected rhesus macaques (n = 4). All five human participants transitioned from daily combination ART to self-administered weekly subcutaneous (SC) injections of 350 mg or 700 mg Leronlimab and to date all participants have sustained virologic suppression for over seven years. In all participants, Leronlimab fully occupied CCR5 receptors on peripheral blood CD4+ T cells and monocytes. In ART-naïve rhesus macaques acutely infected with CCR5-tropic SHIV, weekly SC injections of 50 mg/kg Leronlimab fully suppressed plasma viremia in half of the macaques. CCR5 receptor occupancy by Leronlimab occurred concomitant with rebound of CD4+ CCR5+ T-cells in peripheral blood, and full CCR5 receptor occupancy was found in multiple anatomical compartments. Our results demonstrate that weekly, self-administered Leronlimab was safe, well-tolerated, and efficacious for long-term virologic suppression and should be included in the arsenal of safe, easily administered, longer-acting antiretroviral treatments for people living with HIV-1. Trial Registration: ClinicalTrials.gov Identifiers: NCT02175680 and NCT02355184. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1553-7366 1553-7374 |
| Relation: | https://doaj.org/toc/1553-7366; https://doaj.org/toc/1553-7374 |
| DOI: | 10.1371/journal.ppat.1010396 |
| URL الوصول: | https://doaj.org/article/e58ad860af654e17bfc075a249a3a48a |
| رقم الأكسشن: | edsdoj.58ad860af654e17bfc075a249a3a48a |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 15537366 15537374 |
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| DOI: | 10.1371/journal.ppat.1010396 |