Modified vaccinia virus Ankara undergoes limited replication in human cells and lacks several immunomodulatory proteins:: implications for use as a human vaccine
Modified vaccinia virus Ankara undergoes limited replication in human cells and lacks several immunomodulatory proteins:: implications for use as a human vaccine
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DOI：
10.1099/0022-1317-79-5-1159
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发表时间：
1998-05-01
影响因子：
3.8
通讯作者：
Smith, GL
中科院分区：
文献类型：
--
作者：
Blanchard, TJ;Alcamí, A;Smith, GL
修饰病毒安卡拉（MVA）是一种牛痘病毒（VV）毒株，它通过鸡胚成纤维细胞（CEFs）的连续传代而减毒，与亲本病毒相比含有6个大的基因组缺失。MVA在CEFs中复制良好，但在大多数哺乳动物细胞中复制较差。重组MVA因其宿主范围有限、动物模型免疫原性和无毒性，以及作为天花疫苗的良好安全性记录，是一种很有前景的人痘候选疫苗。在这里，我们提出了MVA的进一步表征，并证明：(i) MVA可以在转化的人类细胞系中复制，尽管很差，但不能在原代人成纤维细胞中复制，尽管细胞间传播有限；（二）MVA是来自原代人细胞的I型干扰素（IFN）的有效诱导剂，可限制病毒在体内的传播；（iii）与其他VV菌株不同，MVA不表达ifn - γ、ifn - α / β、肿瘤坏死因子和CC趋化因子的可溶性受体，但表达可溶性白细胞介素-1 β受体。这为尽管MVA在哺乳动物中复制能力差，但其良好的免疫原性提供了一个合理且可检验的解释。讨论了这些发现对使用MVA作为一种安全的免疫原性人类候选疫苗的意义。
Modified virus Ankara (MVA) is a vaccinia virus (VV) strain that was attenuated by serial passage through chick embryo fibroblasts (CEFs) and contains six large genomic deletions compared with parental virus. MVA replicates well in CEFs, but poorly in most mammalian cells. Recombinant MVA is a promising human vaccine candidate due to its restricted host range, immunogenicity and avirulence in animal models, and excellent safety record as a smallpox vaccine. Here we present a further characterization of MVA and demonstrate that: (i) MVA can replicate, albeit poorly, in transformed human cell lines, but not in primary human fibroblasts although there is limited cell-to-cell spread; (ii) MVA is a potent inducer of type I interferon (IFN) from primary human cells, which may restrict virus spread in vivo; and (iii) unlike other VV strains, MVA does not express soluble receptors for IFN-gamma, IFN-alpha/beta, tumour necrosis factor and CC chemokines, but does express a soluble interleukin-1 beta receptor. This provides a plausible and testable explanation for the good immunogenicity of MVA despite its poor replication in mammals. The implications of these findings for the use of MVA as a safe and immunogenic human vaccine candidate are discussed.