Antibody-based CCR5 blockade protects Macaques from mucosal SHIV transmission

Xiao L. Chang, Gabriela M. Webb, Helen L. Wu, Justin M. Greene, Shaheed Abdulhaqq, Katherine B. Bateman, Jason S. Reed, Cleiton Pessoa, Whitney C. Weber, Nicholas Maier, Glen M. Chew, Roxanne M. Gilbride, Lina Gao, Rebecca Agnor, Travis Giobbi, Jeffrey Torgerson, Don Siess, Nicole Burnett, Miranda Fischer, Oriene Shiel, Cassandra Moats, Bruce Patterson, Kush Dhody, Scott Kelly, Nader Pourhassan, Diogo M. Magnani, Jeremy Smedley, Benjamin N. Bimber, Nancy L. Haigwood, Scott G. Hansen, Timothy R. Brown, Lishomwa C. Ndhlovu () and Jonah B. Sacha ()
Additional contact information
Xiao L. Chang: Vaccine & Gene Therapy Institute
Gabriela M. Webb: Vaccine & Gene Therapy Institute
Helen L. Wu: Vaccine & Gene Therapy Institute
Justin M. Greene: Vaccine & Gene Therapy Institute
Shaheed Abdulhaqq: Vaccine & Gene Therapy Institute
Katherine B. Bateman: Vaccine & Gene Therapy Institute
Jason S. Reed: Vaccine & Gene Therapy Institute
Cleiton Pessoa: Vaccine & Gene Therapy Institute
Whitney C. Weber: Vaccine & Gene Therapy Institute
Nicholas Maier: Vaccine & Gene Therapy Institute
Glen M. Chew: University of Hawaii
Roxanne M. Gilbride: Vaccine & Gene Therapy Institute
Lina Gao: Oregon Health & Science University
Rebecca Agnor: Oregon Health & Science University
Travis Giobbi: Oregon Health & Science University
Jeffrey Torgerson: Oregon Health & Science University
Don Siess: Oregon Health & Science University
Nicole Burnett: Oregon Health & Science University
Miranda Fischer: Oregon Health & Science University
Oriene Shiel: Oregon Health & Science University
Cassandra Moats: Oregon Health & Science University
Bruce Patterson: IncellDX
Kush Dhody: Amarex Clinical Research LLC
Scott Kelly: CytoDyn Inc.
Nader Pourhassan: CytoDyn Inc.
Diogo M. Magnani: MassBiologics of the University of Massachusetts Medical School
Jeremy Smedley: Oregon Health & Science University
Benjamin N. Bimber: Vaccine & Gene Therapy Institute
Nancy L. Haigwood: Vaccine & Gene Therapy Institute
Scott G. Hansen: Vaccine & Gene Therapy Institute
Timothy R. Brown: Palm Springs
Lishomwa C. Ndhlovu: Weill Cornell Medicine
Jonah B. Sacha: Vaccine & Gene Therapy Institute

Nature Communications, 2021, vol. 12, issue 1, 1-11

Abstract: 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 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.

Date: 2021
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DOI: 10.1038/s41467-021-23697-6

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