Live virus vaccines based on a vesicular stomatitis virus (VSV) backbone: Standardized template with key considerations for a risk/benefit assessment
Live virus vaccines based on a vesicular stomatitis virus (VSV) backbone: Standardized template with key considerations for a risk/benefit assessment
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DOI：
10.1016/j.vaccine.2016.06.071
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发表时间：
2016-12-12
期刊：
影响因子：
5.5
通讯作者：
Chen, Robert T.
中科院分区：
文献类型：
--
作者：
Clarke, David K.;Hendry, R. Michael;Chen, Robert T.
布莱顿协作病毒载体疫苗安全工作组（V3SWG）的成立是为了评估活体，重组病毒疫苗的安全性，在其基因组中纳入了来自异源性病毒和其他微生物病原体的基因（所谓的“ Chimeric病毒疫苗）”）。许多这样的病毒载体疫苗现在处于临床评估的各个阶段。在这里，我们引入了一种重组囊泡口腔炎病毒（RVSV）作为HIV-1的潜在嵌合病毒疫苗的衰减形式，其影响是用作其他病原体的疫苗载体。通过结合两个主要基因组修饰，将RVSV/HIV-1疫苗载体减弱。这些修饰具有协同作用，以极大地增强载体衰减，而由此产生的RVSV载体在敏感的小鼠和非人类灵长类动物神经电动机模型中表现出安全性。该表达HIV-1 GAG蛋白的载体已在两期临床试验中完成评估。在一项试验中，RVSV/HIV-1载体用于同源的两剂量方案，并在第二次试验中与PDNA进行了异源质量增强方案。在任何一项试验中，均未在疫苗接种后在血液，尿液或唾液中检测到载体，也没有发生严重的不良事件。在两种试验中诱导了插孔特异性免疫反应，在Prime Boost方案中检测到的频率T细胞反应最高。 RVSV/HIV-1载体在HIV-1阳性参与者中正在进行的I期试验中也证明了安全性。此外，已经使用表达HIV-1 Env的RVSV矢量生产了临床试验材料，并且I期临床评估将在2016年初开始。在本文中，我们使用了描述新型RVSV疫苗媒介的关键特征的标准化模板，即与野生型VSV相比。该模板通过提高信息的透明度和可比性来促进主要利益相关者之间的科学话语。布莱顿协作V3SWG模板也可能是评估其他重组病毒载体疫苗的指南。由Elsevier Ltd.出版。
The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) was formed to evaluate the safety of live, recombinant viral vacci2;nes incorporating genes from heterologous viral and other microbial pathogens in their genome (so-called "chimeric virus vaccines"). Many such viral vector vaccines are now at various stages of clinical evaluation. Here, we introduce an attenuated form of recombinant vesicular stomatitis virus (rVSV) as a potential chimeric virus vaccine for HIV-1, with implications for use as a vaccine vector for other pathogens. The rVSV/HIV-1 vaccine vector was attenuated by combining two major genome modifications. These modifications acted synergistically to greatly enhance vector attenuation and the resulting rVSV vector demonstrated safety in sensitive mouse and non-human primate neurovirulence models. This vector expressing HIV-1 gag protein has completed evaluation in two Phase I clinical trials. In one trial the rVSV/HIV-1 vector was administered in a homologous two-dose regimen, and in a second trial with pDNA in a heterologous prime boost regimen. No serious adverse events were reported nor was vector detected in blood, urine or saliva post vaccination in either trial. Gag specific immune responses were induced in both trials with highest frequency T cell responses detected in the prime boost regimen. The rVSV/HIV-1 vector also demonstrated safety in an ongoing Phase I trial in HIV-1 positive participants. Additionally, clinical trial material has been produced with the rVSV vector expressing HIV-1 env, and Phase I clinical evaluation will initiate in the beginning of 2016. In this paper, we use a standardized template describing key characteristics of the novel rVSV vaccine vectors, in comparison to wild type VSV. The template facilitates scientific discourse among key stakeholders by increasing transparency and comparability of information. The Brighton Collaboration V3SWG template may also be useful as a guide to the evaluation of other recombinant viral vector vaccines. Published by Elsevier Ltd.