A fusion protein of HCMV IE1 exon4 and IE2 exon5 stimulates potent cellular immunity in an MVA vaccine vector.
A fusion protein of HCMV IE1 exon4 and IE2 exon5 stimulates potent cellular immunity in an MVA vaccine vector.
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DOI：
10.1016/j.virol.2008.04.034
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发表时间：
2008-08
期刊：
影响因子：
3.7
通讯作者：
Zhongde Wang;Wendi Zhou;T. Srivastava;C. L. Rosa;Angelo Mandarino;Stephen J. Forman;J. A. Zaia;William J. Britt;Don J. Diamond
中科院分区：
文献类型：
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作者：
Zhongde Wang;Wendi Zhou;T. Srivastava;C. L. Rosa;Angelo Mandarino;Stephen J. Forman;J. A. Zaia;William J. Britt;Don J. Diamond
一种含有能够引发细胞免疫反应的抗原库的治疗性CMV疫苗尚未成功地应用于已经感染的患者。为了解决这个问题，我们开发了一种来自改良安卡拉痘苗病毒(MVA)的候选疫苗，它表达CMV的三个免疫优势抗原(pp65，IE1，IE2)。该疫苗的创新之处在于融合了CMV即刻早期区域的两个相邻外显子，它们在MVA中成功表达，在初级和记忆反应模型中都具有强大的免疫原性。在小鼠模型中对病毒疫苗的免疫原性评价表明，它能刺激针对所有这三种抗原的初级免疫，包括在CD4+和CD8+T细胞亚群中。在接受造血细胞移植后6个月内，对健康CMV阳性捐赠者或患者的人PBMC的评估显示，对现有的CMV特异性CD4+和CD8+T细胞亚群有很强的刺激作用。
A therapeutic CMV vaccine incorporating an antigenic repertoire capable of eliciting a cellular immune response has yet to be successfully implemented for patients who already have acquired an infection. To address this problem, we have developed a vaccine candidate derived from modified vaccinia Ankara (MVA) that expresses three immunodominant antigens (pp65, IE1, IE2) from CMV. The novelty of this vaccine is the fusion of two adjacent exons from the immediate-early region of CMV, their successful expression in MVA, and robust immunogenicity in both primary and memory response models. Evaluation of the immunogenicity of the viral vaccine in mouse models shows that it can stimulate primary immunity against all three antigens in both the CD4+and CD8+T cell subsets. Evaluation of human PBMC from healthy CMV-positive donors or patients within 6 months of receiving hematopoietic cell transplant shows robust stimulation of existing CMV-specific CD4+and CD8+T cell subsets.