Nature communications · 2021
Antibody-based CCR5 blockade protects Macaques from mucosal SHIV transmission.
СтатьяПоддержка NIH: внешняя программаНазвание и аннотация: Перевод пока не подготовлен
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Chang Xiao L, Webb Gabriela M, Wu Helen L, Greene Justin M, Abdulhaqq Shaheed, Bateman Katherine B, Reed Jason S, Pessoa Cleiton, Weber Whitney C, Maier Nicholas, Chew Glen M, Gilbride Roxanne M, Gao Lina, Agnor Rebecca, Giobbi Travis, Torgerson Jeffrey, Siess Don, Burnett Nicole, Fischer Miranda, Shiel Oriene, Moats Cassandra, Patterson Bruce, Dhody Kush, Kelly Scott, Pourhassan Nader, Magnani Diogo M, Smedley Jeremy, Bimber Benjamin N, Haigwood Nancy L, Hansen Scott G, Brown Timothy R, Ndhlovu Lishomwa C, Sacha Jonah B
Аннотация
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.