【佳音】HIV候选疫苗临床前试验大获成功

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作为研究和开发基于病毒颗粒的疫苗（virosome-based vaccine）以便阻止人类传染病通过粘膜进行传播的先驱者，Mymetics公司本周一（4月11日）宣布作为临床前研究的一部分，它的创新性的HIV候选疫苗经证实能够让每组12只雌性猴子的群体显著地抵抗反复性HIV病毒暴露。
这项盲法研究是由美国德州生物医学艾滋病研究项目（Texas Biomed AIDS Research Program）科学家兼主任Ruth Ruprecht博士领导的，而且获得比尔与美琳达-盖茨基金会资金资助。在这项研究的第一部分，Mymetics公司的这种基于病毒颗粒的双组分HIV疫苗能够显著延缓持续性感染建立时间的效率为87%，而对照组雌性猴子在7次阴道内病毒攻击后就建立持续性感染。这项研究旨在模拟女性接触来自HIV感染男性的精液，不过在这7次动物阴道内病毒攻击中，每次的病毒攻击剂量大约是在性活动期间由一名HIV感染男性传播给一名未感染女性的平均HIV剂量的7万倍。

在这项研究的第二部分中，从第8次病毒攻击开始，雌性猴子病毒攻击剂量增加了50%，是由一名HIV感染男性传播给一名女性伴侣的平均HIV剂量的10万多倍。在这种病毒攻击剂量下，这种HIV候选疫苗并不会显著保护这些动物，这是因为它们的免疫系统超负荷运载。

Ruth Ruprecht博士说，“我们为这种HIV候选疫苗提供的初步强大保护感到鼓舞。这也与在中国进行的一项早期的研究中的结果相一致。这种疫苗诱导的免疫防御最终被HIV打败的事实还需要进行详细分析以便理解这种疫苗的初步作用机制和了解其他的哪些免疫防御能够被用来产生更加强效的抗病毒作用。”

Mymetics公司销售总监Sylvain Fleury评论道，“我们非常高兴Mymetics公司开发的基于病毒颗粒的HIV疫苗可能能够在模拟男性到女性间性传播的条件下阻止病毒传播。特别是考虑到这些保护结果来自两个不同的国家进行的两项研究，而且这两项研究涉及两种不同的恒河猴亚种，采用两种不同的疫苗批号，没有加入佐剂。这些保护效果是在不同的居住和环境条件下在遗传不同的动物中观察到的，这就为这些观察结果提出更加强有力的证据。”

Mymetics公司首席执行官Ronald Kempers说，“我们对Ruprecht博士团队（包括Samir Lakhashe博士）的专业化和深入细致的研究工作印象深刻，并且期待理解我们的疫苗的作用机制。这项研究证实我们的HIV候选疫苗在真实情境下能够提供保护，而且它强力地提示着它可能保护女性免受HIV性传播，为在未来开发一种有效的HIV疫苗更接近一步。病毒颗粒在儿童和成年人中具有较强的安全记录，而且我们构造出的病毒颗粒能够容易地与其他的候选疫苗和治疗药物相结合，因此我们希望我们能够吸引资金用于临床开发，从而为开发一种HIV疫苗更接近一步。”

这项研究以36只印度恒河猴（Indian origin rhesus macaque）---每12只动物为一组以便具有更强的统计能力---为实验对象，比较两种HIV抗原接种策略和安慰剂，随后让这些动物遭受阴道内活的异源HIV毒株攻击。

这项研究旨在复制中国医学科学院医学实验动物研究所（ILAS）早前成功完成的一项较为小型的研究，其中在这项小型研究中，一种双组分HIV疫苗保护所有的中国恒河猴（Chinese rhesus macaque）抵抗反复病毒暴露而不会遭受持续性感染---这是一个前所未有的结果（Immunity, 25 February 2011, 34(2):269–280, doi: 10.1016/j.immuni.2011.01.015）。在针对人志愿者开展的I期临床试验中，这种双组分疫苗中的一种组分（一种gp41肽）进一步表现出较强的安全性和耐受性记录（PLoS ONE, 20 February 2013, doi: 10.1371/journal.pone.0055438）。

作为利用Mymetics公司拥有的病毒颗粒专利技术生产的HIV-1候选疫苗，该公司旨在提供基于黏膜保护的第一道防线，而且也提供基于血液抗体产生的第二道抗感染防线。Mymetics公司已生产了液体形式的HIV疫苗用于临床试验，而且自去年以来，在欧洲地平线2020计划（European Horizon 2020 Program，它的MACIVIVA项目编号为646122）的资助下，正在开发新一代无针注射的采用冷藏链（cold chain）的病毒颗粒疫苗，这种疫苗可能非常适合用于发展中国家。

题目：Mymetics' HIV vaccine candidate confirms promise in preclinical study
Mymetics Corporation, a pioneer in the research and development of virosome-based vaccines to prevent transmission of human infectious diseases across mucosal membranes, announced today that its innovative HIV vaccine candidate has shown to generate significant protection in groups of twelve female monkeys against repeated AIDS virus exposures during part of the preclinical study.

The blinded study was led by Dr. Ruth Ruprecht, Scientist & Director of the Texas Biomed AIDS Research Program and was funded by the Bill & Melinda Gates foundation. During the first part of the study the Mymetics' two-component virosome-based HIV vaccine was able to show significant efficacy of 87% in delaying the time to persistent infection versus the control group after 7 intravaginal virus challenges. The study aimed to mimic the exposure of women to semen from HIV-infected men, although the viral dose of each of these 7 animal challenges represented about 70,000 times the average human HIV dose passed during sexual intercourse from an HIV-infected male to an uninfected female.

During the second part of the study the animal viral challenge dose was increased by 50% starting from the 8th challenge onward, reaching more than 100,000 times the average amount of virus passed from an infected man to a female partner. At this virus dose, the vaccine did not show significant protection in the animals as the immune system was overloaded.

Dr. Ruth Ruprecht said, "We are encouraged by the initial strong protection provided by the vaccine candidate, which is in line with the results from an earlier primate study performed in China that we were asked to repeat. The fact that the vaccine-induced immune defenses were eventually overcome requires a careful analysis to understand the mechanisms of the initial vaccine action and to learn what other immune defenses can be enlisted to yield even more potent antiviral action."
Sylvain Fleury, CSO of Mymetics, commented, "We are pleased that Mymetics HIV virosome-based vaccine could strongly prevent virus transmission under conditions that mimic male-to female sexualtransmission. Especially as these protection results are coming from two studies conducted in two different countries, with two different sub-species of macaques, with different vaccine lots and without an adjuvant. The observed protection in genetically different animals raised in different housing and environmental conditions gives more weight to these observations."
Ronald Kempers, CEO of Mymetics, "We were very impressed with the professional and thorough work delivered by Dr. Ruprecht's team, including Dr. Samir Lakhashe, Staff Scientist at Texas Biomed, and look forward to understanding the mechanisms of action of our vaccine. This study proves that our HIV vaccine candidate can protect in very realistic settings and it provides a strong indication to possibly protect women against sexually transmitted HIV and come closer to an effective HIV vaccine in the future. Virosomes have a strong safety profile in children and adults and our virosome construct can easily be combined with other vaccine candidates and treatments, therefore we are hopeful that we can attract funding for the clinical development and move a step closer to an HIV vaccine."
The study involved 36 Indian origin rhesus macaques (monkeys) with 12 animals per group for more statistical power, compared two antigen vaccination regimens with placebo and was followed by intra-vaginal heterologous challenges with live virus.
This study was designed to replicate a successfully completed smaller study at the Institute of Laboratory Animal Science (ILAS) in Beijing, China in which the two-component vaccine protected all Chinese rhesus macaque monkeys against repeated virus exposures from persistent infection - an unprecedented result (1). One of the vaccine components further showed a strong safety and tolerance profile in a Phase I clinical trial in human volunteers .
With its HIV-1 (human immunodeficiency virus type 1) vaccine candidate, produced through its proprietary virosome technology, Mymetics aims to provide both a first line of defense through mucosal protection as well as a second line of defense against infection through the generation of blood antibodies. Mymetics has produced the tested HIV vaccine construct for clinical trials in liquid form and, since last year, is developing a new generation of needle-free and cold chain independent virosomal vaccine construct with the support of the European Horizon 2020 Program (MACIVIVA Project no. 646122), which would be very suitable for developing countries.

原文出处：http://medicalxpress.com/news/20 ... te-preclinical.html

本文来源：生物谷