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改良基于 NYVAC 的疫苗载体。

Improved NYVAC-based vaccine vectors.

机构信息

The Biodesign Institute at Arizona State University, Tempe, Arizona, United States of America.

出版信息

PLoS One. 2011;6(11):e25674. doi: 10.1371/journal.pone.0025674. Epub 2011 Nov 9.

DOI:10.1371/journal.pone.0025674
PMID:22096477
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3212513/
Abstract

While as yet there is no vaccine against HIV/AIDS, the results of the phase III Thai trial (RV144) have been encouraging and suggest that further improvements of the prime/boost vaccine combination of a poxvirus and protein are needed. With this aim, in this investigation we have generated derivatives of the candidate vaccinia virus vaccine vector NYVAC with potentially improved functions. This has been achieved by the re-incorporation into the virus genome of two host range genes, K1L and C7L, in conjunction with the removal of the immunomodulatory viral molecule B19, an antagonist of type I interferon action. These novel virus vectors, referred to as NYVAC-C-KC and NYVAC-C-KC-ΔB19R, have acquired relevant biological characteristics, giving higher levels of antigen expression in infected cells, replication-competency in human keratinocytes and dermal fibroblasts, activation of selective host cell signal transduction pathways, and limited virus spread in tissues. Importantly, these replication-competent viruses have been demonstrated to maintain a highly attenuated phenotype.

摘要

虽然目前尚无针对艾滋病毒/艾滋病的疫苗，但 III 期泰国试验（RV144）的结果令人鼓舞，表明需要进一步改进痘病毒和蛋白的初免-加强疫苗组合。为此，在这项研究中，我们生成了候选痘苗病毒疫苗载体 NYVAC 的衍生物，这些衍生物具有潜在的改进功能。这是通过将两个宿主范围基因 K1L 和 C7L 重新整合到病毒基因组中，并同时去除免疫调节病毒分子 B19（I 型干扰素作用的拮抗剂）来实现的。这些新型病毒载体被称为 NYVAC-C-KC 和 NYVAC-C-KC-ΔB19R，它们获得了相关的生物学特性，在感染细胞中表达更高水平的抗原，在人角质形成细胞和真皮成纤维细胞中具有复制能力，激活选择性宿主细胞信号转导途径，并在组织中限制病毒传播。重要的是，这些具有复制能力的病毒已被证明保持高度减毒表型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4491/3212513/7c5d5de67ed9/pone.0025674.g008.jpg
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