Suppression of human and simian immunodeficiency virus replication with the CCR5-specific antibody Leronlimab in two species
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Published:2022-03-31
Issue:3
Volume:18
Page:e1010396
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ISSN:1553-7374
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Container-title:PLOS Pathogens
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language:en
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Short-container-title:PLoS Pathog
Author:
Chang Xiao L., Reed Jason S., Webb Gabriela M., Wu Helen L., Le Jimmy, Bateman Katherine B., Greene Justin M., Pessoa Cleiton, Waytashek Courtney, Weber Whitney C., Hwang Joseph, Fischer Miranda, Moats Cassandra, Shiel Oriene, Bochart Rachele M., Crank Hugh, Siess Don, Giobbi Travis, Torgerson Jeffrey, Agnor Rebecca, Gao Lina, Dhody Kush, Lalezari Jacob P., Bandar Ivo Sah, Carnate Alnor M., Pang Alina S., Corley Michael J., Kelly Scott, Pourhassan Nader, Smedley Jeremy, Bimber Benjamin N., Hansen Scott G., Ndhlovu Lishomwa C., Sacha Jonah B.ORCID
Abstract
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.
Funder
National Institutes of Health CytoDyn
Publisher
Public Library of Science (PLoS)
Subject
Virology,Genetics,Molecular Biology,Immunology,Microbiology,Parasitology
Cited by
9 articles.
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