Antibody profiling by proteome microarray reveals the immunogenicity of the attenuated smallpox vaccine modified vaccinia virus Ankara is comparable to that of Dryvax
Antibody profiling by proteome microarray reveals the immunogenicity of the attenuated smallpox vaccine modified vaccinia virus Ankara is comparable to that of Dryvax
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DOI：
10.1128/jvi.01706-07
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发表时间：
2008-01-01
影响因子：
5.4
通讯作者：
Felgner, Philip L.
中科院分区：
文献类型：
--
作者：
Davies, D. Huw;Wyatt, Linda S.;Felgner, Philip L.
改良的安卡拉牛痘病毒（MVA）是一种高度减毒的牛痘病毒，正在考虑作为传统天花疫苗Dryvax的替代品。通过安卡拉痘病毒在鸡胚成纤维细胞中的广泛传代，可以减弱MVA。一些免疫调节基因和影响宿主范围的基因被删除或突变，在大多数非禽类细胞中，复制在感染的后期阶段被中止。这些突变对免疫原性的影响尚不清楚。由于MVA中的结构基因似乎是完整的，因此假设保留了抗体中和的关键靶标。为了测试这一点，我们探测了西储（WR）蛋白质组与MVA和Dryvax疫苗接种后的人和猕猴的血清的微阵列。由于MVA的大多数蛋白质序列与其他牛痘病毒株的蛋白质序列具有97 - 99%的同一性，因此预期广泛的结合交叉反应性，除了那些缺失或截短的。尽管不同的宿主和免疫方案，MVA和Dryvax抗体谱大致相似，针对膜和核心蛋白的抗体是最保守的。对非结构蛋白的反应保守性较差，尽管这些反应预计不会影响病毒中和。最广泛的抗体反应，获得了超免疫兔WR，这是在兔子的致病性。这些数据表明，尽管MVA中存在突变和缺失，但其总体免疫原性与Dryvax大致相当，特别是在膜蛋白抗体水平上。这项工作支持了其他信息，表明MVA可能是Dryvax的有用替代品。
Modified vaccinia virus Ankara (MVA) is a highly attenuated vaccinia virus that is under consideration as an alternative to the conventional smallpox vaccine Dryvax. MVA was attenuated by extensive passage of vaccinia virus Ankara in chicken embryo fibroblasts. Several immunomodulatory genes and genes that influence host range are deleted or mutated, and replication is aborted in the late stage of infection in most nonavian cells. The effect of these mutations on immunogenicity is not well understood. Since the structural genes appear to be intact in MVA, it is hypothesized that critical targets for antibody neutralization have been retained. To test this, we probed microarrays of the Western Reserve (WR) proteome with sera from humans and macaques after MVA and Dryvax vaccination. As most protein sequences of MVA are 97 to 99% identical to those of other vaccinia virus strains, extensive binding cross-reactivity is expected, except for those deleted or truncated. Despite different hosts and immunization regimens, the MVA and Dryvax antibody profiles were broadly similar, with antibodies against membrane and core proteins being the best conserved. The responses to nonstructural proteins were less well conserved, although these are not expected to influence virus neutralization. The broadest antibody response was obtained for hyperimmune rabbits with WR, which is pathogenic in rabbits. These data indicate that, despite the mutations and deletions in MVA, its overall immunogenicity is broadly comparable to that of Dryvax, particularly at the level of antibodies to membrane proteins. The work supports other information suggesting that MVA may be a useful alternative to Dryvax.