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长效衣壳抑制剂可保护猕猴免受反复的SHIV感染
作者:小柯机器人 发布时间:2021/12/11 14:50:45

美国哈佛医学院Dan H. Barouch、吉列德公司Stephen R. Yant等研究人员合作发现,长效衣壳抑制剂可保护猕猴免受反复的SHIV感染。相关论文于2021年12月7日在线发表于国际学术期刊《自然》。

研究人员表示,由于目前还没有预防HIV感染的疫苗,使用抗逆转录病毒药物(ARV)的暴露前预防(PrEP)是防治HIV流行的一个重要工具。长效抗逆转录病毒药物有望在目前必须每天服用的PrEP策略的基础上,通过减少给药频率而取得成功。GS-CA1是一种小分子HIV衣壳抑制剂,对广泛的HIV毒株具有皮摩尔的抗病毒效力,包括对现有抗逆转录病毒药物有抵抗力的变种,并在HIV感染的小鼠模型中显示出长效治疗潜力。

研究人员发现,单次皮下注射GS-CA1可长期保护猕猴免受反复的直肠SHIV感染。所有的对照动物在15次每周的挑战后都会被感染,而单次300mg/kg剂量的GS-CA1能在24周内提供97%的暴露感染风险降低。药代动力学分析显示,GS-CA1血浆浓度与SHIV挑战保护之间存在关联,GS-CA1水平大于恒河猴血浆蛋白调整后95%有效浓度的2倍,并在该模型中提供100%的保护。这些概念验证数据支持将衣壳抑制剂作为一种新的长效PrEP策略在人类中发展。

附:英文原文

Title: Long Acting Capsid Inhibitor Protects Macaques From Repeat SHIV Challenges

Author: Vidal, Samuel J., Bekerman, Elena, Hansen, Derek, Lu, Bing, Wang, Kelly, Mwangi, Judy, Rowe, William, Campigotto, Federico, Zheng, Jim, Kato, Darryl, Chandrashekar, Abishek, Barrett, Julia, Patel, Shivani, Wan, Huahua, Anioke, Tochi, Mercado, Noe B., Nkolola, Joseph P., Ferguson, Melissa J., Rinaldi, William J., Callebaut, Christian, Blair, Wade, Cihlar, Tomas, Geleziunas, Romas, Yant, Stephen R., Barouch, Dan H.

Issue&Volume: 2021-12-07

Abstract: Since there is currently no vaccine that prevents HIV infection, pre-exposure prophylaxis (PrEP) with antiretrovirals (ARVs) is an important tool in combating the HIV pandemic1,2. Long-acting ARVs promise to build on the success of current PrEP strategies, which must be taken daily, by reducing the frequency of administration3. GS-CA1 is a small-molecule HIV capsid inhibitor with picomolar antiviral potency against a broad array of HIV strains, including variants resistant to existing ARVs, and has shown long-acting therapeutic potential in a mouse model of HIV infection4. Here we show that a single subcutaneous administration of GS-CA1 provides long-term protection against repeated rectal SHIV challenges in rhesus macaques. Whereas all control animals became infected after 15 weekly challenges, a single 300 mg/kg dose of GS-CA1 provided 97% per-exposure risk reduction for infection for 24 weeks. Pharmacokinetic analysis showed a correlation between GS-CA1 plasma concentration and protection from SHIV challenges, with GS-CA1 levels >2-fold the rhesus plasma protein-adjusted 95% effective concentration conferring 100% protection in this model. These proof-of-concept data support the development of capsid inhibitors as a novel long-acting PrEP strategy in humans.

DOI: 10.1038/s41586-021-04279-4

Source: https://www.nature.com/articles/s41586-021-04279-4

期刊信息

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html