抗体介导的 CCR5 阻断可保护猕猴免受黏膜 SHIV 传播。
Antibody-based CCR5 blockade protects Macaques from mucosal SHIV transmission.
机构信息
Vaccine & Gene Therapy Institute, Portland, OR, USA.
Oregon National Primate Research Center, Oregon Health & Science University, Portland, OR, USA.
出版信息
Nat Commun. 2021 Jun 7;12(1):3343. doi: 10.1038/s41467-021-23697-6.
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 SHIV. 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.
在缺乏预防性疫苗的情况下，使用抗逆转录病毒疗法（ART）作为暴露前预防（PrEP），以防止未感染个体获得 HIV，这是减缓艾滋病流行的一种有前途的方法，但由于患者不完全依从性和抗 ART 变异体的存在，其疗效受到阻碍。在这里，我们报告说，通过 CCR5 特异性抗体 Leronlimab 对 HIV Env-CCR5 结合的竞争性抑制作用，可保护恒河猴免受 CCR5 嗜性 SHIV 的重复直肠内攻击后感染。每周注射 10mg/kg 的 Leronlimab 可提供显著但部分保护，而每两周注射 50mg/kg 可完全防止 SHIV 获得。接受挑战后的受保护猕猴的组织活检显示完全 CCR5 受体占据和不存在病毒核酸。在 Leronlimab 洗脱后，受保护的猕猴仍保持无病毒血症，并且将血液细胞过继转移到未感染的猕猴中不会传播病毒感染。这些数据表明，用 Leronlimab 阻断 CCR5 是一种有前途的 HIV 预防方法，并支持启动临床试验。
Zotero 插件