2012年12月8日 訊 /生物谷BIOON/ --近日,，刊登在國際雜志PLOS Pathogens上的一篇研究報告中,，來自歐洲聯(lián)合高效抗逆轉(zhuǎn)錄病毒殺微生物劑協(xié)會的研究者通過對非靈長類動物模型進行研究揭示，一種殺微生物劑的凝膠可以有效抵御AIDS病毒的感染,。研究者描述了這種凝膠的關(guān)鍵成分是一種小分子的多肽,，其可以作為誘餌來與病毒結(jié)合，并且抑制艾滋病毒感染機體細(xì)胞,。
目前在世界范圍內(nèi),，科學(xué)家都在致力于開發(fā)出新型的抵御HIV感染的疫苗，與此同時,，很多研究者也在研究用殺微生物劑的凝膠來降低HIV的傳播和感染,。截止目前，一些抵御病毒進入機體細(xì)胞的療法表現(xiàn)出潛在的個體保護作用,。
本文研究中,，研究者使用了名為“miniCD4s”的工程化肽類，因為其可以模仿CD4細(xì)胞的受體來使用,，CD4受體是HIV細(xì)胞進入機體免疫細(xì)胞的通道,。研究揭示了miniCD4s可以阻止HIV病毒進入到動物模型的離體細(xì)胞中。研究者在殺微生物劑的凝膠中添加入0.3%的miniCD4s,，并且將其植入到6只雌性短尾猴的陰道中,，隨后研究者給短尾猴的陰道中注入高劑量的HIV病毒，這個劑量足以使得短尾猴感染,，但是結(jié)果顯示,，6只短尾猴中有5只都沒有被HIV感染，而且在機體組織中也沒有發(fā)現(xiàn)HIV感染的蹤跡,。也不能在其血漿中檢測出任何病毒的抗體,，這就揭示了,，這種殺微生物劑的凝膠（含miniCD4s）的確可以抑制HIV的感染。
這項研究為我們開發(fā)抑制HIV,，保護個體的療法提供了幫助和希望,，后期研究者將會進行臨床上的試驗進一步揭示其研究成果。（生物谷Bioon.com）
doi:10.1371/journal.ppat.1003071
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MiniCD4 Microbicide Prevents HIV Infection of Human Mucosal Explants and Vaginal Transmission of SHIV162P3 in Cynomolgus Macaques
Nathalie Dereuddre-Bosquet1,2, Laurence Morellato-Castillo3, Joachim Brouwers4, Patrick Augustijns4, Kawthar Bouchemal5, Gilles Ponchel5, Oscar H. P. Ramos3, Carolina Herrera6, Martha Stefanidou7, Robin Shattock6, Leo Heyndrickx8, Guido Vanham8, Pascal Kessler3, Roger Le Grand1,2, Loïc Martin3*
In complement to an effective vaccine, development of potent anti-HIV microbicides remains an important priority. We have previously shown that the miniCD4 M48U1, a functional mimetic of sCD4 presented on a 27 amino-acid stable scaffold, inhibits a broad range of HIV-1 isolates at sub-nanomolar concentrations in cellular models. Here, we report that M48U1 inhibits efficiently HIV-1Ba-L in human mucosal explants of cervical and colorectal tissues. In vivo efficacy of M48U1 was evaluated in nonhuman primate (NHP) model of mucosal challenge with SHIV162P3 after assessing pharmacokinetics and pharmacodynamics of a miniCD4 gel formulation in sexually matured female cynomolgus macaques. Among 12 females, half were treated with hydroxyethylcellulose-based gel (control), the other half received the same gel containing 3 mg/g of M48U1, one hour before vaginal route challenge with 10 AID50 of SHIV162P3. All control animals were infected with a peak plasma viral load of 105–106 viral RNA (vRNA) copies per mL. In animals treated with miniCD4, 5 out of 6 were fully protected from acquisition of infection, as assessed by qRT-PCR for vRNA detection in plasma, qPCR for viral DNA detection in PBMC and lymph node cells. The only infected animal in this group had a delayed peak of viremia of one week. These results demonstrate that M48U1 miniCD4 acts in vivo as a potent entry inhibitor, which may be considered in microbicide developments.
