Antibody-based CCR5 blockade protects Macaques from mucosal SHIV transmission

Autor: Bruce K. Patterson, Whitney C. Weber, Gabriela M. Webb, Katherine B. Bateman, Cleiton Pessoa, Shaheed A. Abdulhaqq, Lina Gao, Benjamin N. Bimber, Jonah B. Sacha, Scott G. Hansen, Xiao L. Chang, Justin M. Greene, Kush Dhody, Scott Kelly, Nancy L. Haigwood, Rebecca Agnor, Cassandra Moats, Glen M. Chew, Roxanne M. Gilbride, Jeremy Smedley, Nicole D Burnett, Oriene Shiel, Nicholas Maier, Don Siess, Lishomwa C. Ndhlovu, Miranda Fischer, Timothy R. Brown, Diogo M. Magnani, Jason S. Reed, Travis Giobbi, Jeffrey Torgerson, Helen L. Wu, Nader Pourhassan
Jazyk: angličtina
Rok vydání: 2021
Předmět:
CD4-Positive T-Lymphocytes
Male
0301 basic medicine
Adoptive cell transfer
Receptors
CCR5
Chemokine receptor CCR5
viruses
Science
Simian Acquired Immunodeficiency Syndrome
General Physics and Astronomy
HIV Infections
CD8-Positive T-Lymphocytes
HIV Antibodies
Antibodies
Monoclonal
Humanized
Article
General Biochemistry
Genetics and Molecular Biology
03 medical and health sciences
0302 clinical medicine
Animals
Humans
Medicine
030212 general & internal medicine
Hiv acquisition
Mucous Membrane
Multidisciplinary
biology
business.industry
Transmission (medicine)
virus diseases
General Chemistry
Viral Load
Macaca mulatta
Antiretroviral therapy
Virology
Blockade
Clinical trial
030104 developmental biology
biology.protein
Female
Pre-Exposure Prophylaxis
Simian Immunodeficiency Virus
Antibody therapy
Antibody
business
Zdroj: Nature Communications, Vol 12, Iss 1, Pp 1-11 (2021)
Nature Communications
ISSN: 2041-1723
Popis: In the absence of a prophylactic vaccine, the use of antiretroviral therapy (ART) as pre-exposure prophylaxis (PrEP) to prevent HIV acquisition by uninfected individuals is a promising approach to slowing the epidemic, but its efficacy is hampered by incomplete patient adherence and ART-resistant variants. Here, we report that competitive inhibition of HIV Env-CCR5 binding via the CCR5-specific antibody Leronlimab protects rhesus macaques against infection following repeated intrarectal challenges of CCR5-tropic SHIVSF162P3. Injection of Leronlimab weekly at 10 mg/kg provides significant but partial protection, while biweekly 50 mg/kg provides complete protection from SHIV acquisition. Tissue biopsies from protected macaques post challenge show complete CCR5 receptor occupancy and an absence of viral nucleic acids. After Leronlimab washout, protected macaques remain aviremic, and adoptive transfer of hematologic cells into naïve macaques does not transmit viral infection. These data identify CCR5 blockade with Leronlimab as a promising approach to HIV prophylaxis and support initiation of clinical trials.
CCR5 is a co-receptor for many transmitted HIV strains. Here, the authors show that biweekly injection of the CCR5-specific antibody Leronlimab protects rhesus macaques against infection following repeated intrarectal challenges of a CCR5-tropic SHIV.
Databáze: OpenAIRE
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