@article{ad6e10c9f7f747c28d891937d929674d,
title = "Antibody-based CCR5 blockade protects Macaques from mucosal SHIV transmission",
abstract = "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 na{\"i}ve 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.",
author = "Chang, {Xiao L.} and Webb, {Gabriela M.} and Wu, {Helen L.} and Greene, {Justin M.} and Shaheed Abdulhaqq and Bateman, {Katherine B.} and Reed, {Jason S.} and Cleiton Pessoa and Weber, {Whitney C.} and Nicholas Maier and Chew, {Glen M.} and Gilbride, {Roxanne M.} and Lina Gao and Rebecca Agnor and Travis Giobbi and Jeffrey Torgerson and Don Siess and Nicole Burnett and Miranda Fischer and Oriene Shiel and Cassandra Moats and Bruce Patterson and Kush Dhody and Scott Kelly and Nader Pourhassan and Magnani, {Diogo M.} and Jeremy Smedley and Bimber, {Benjamin N.} and Haigwood, {Nancy L.} and Hansen, {Scott G.} and Brown, {Timothy R.} and Ndhlovu, {Lishomwa C.} and Sacha, {Jonah B.}",
note = "Funding Information: We thank Nancy Miller for providing the in vivo characterized SHIVSF162P3 challenge stock and the dedicated animal care staff at ONPRC. We acknowledge the contribution of the Hawaii Center for AIDS, Director, Dr. Cecilia Shikuma and the Leukapharesis team at Queens Medical Center for support and commitment in specimen sampling from the study participant. Reagents used in these studies were provided by the NIH Nonhuman Primate Reagent Resource. The following reagent was obtained through the AIDS Reagent Program, Division of AIDS, NIAID, NIH: human IL-2 from La Roche and the HIV-1 60 International Isolate Panel. We acknowledge the macaques that contributed to this study. This manuscript is dedicated to Timothy Ray Brown, who inspired, supported, and materially contributed to this research. Macaque icons used in Fig. 2a were created on BioRender.com. This work is supported by National Institute of Allergy and Infectious Diseases (NIAID) grants R01 AI129703, R01 AI54559, and R21 AI54559 to J.B.S., K01 OD026561 to J.M.G., U24 AI126683 to D.M.M., and the Oregon National Primate Research Center Core grant P51 OD011092 from the National Institutes of Health, Office of the Director. Publisher Copyright: {\textcopyright} 2021, The Author(s).",
year = "2021",
month = dec,
day = "1",
doi = "10.1038/s41467-021-23697-6",
language = "English (US)",
volume = "12",
journal = "Nature communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}