The FP9 strain of F has been described as a more immunogenic recombinant vaccine vector than the Webster FPV-M (FPW) strain (R. J. Anderson et al., J. Immunol. 172:3094-3100, 2004). This study expands the comparison to include two separate recombinant antigens and multiple, rather than single, independent viral clones derived from the two strains. Dual-poxvirus heterologous prime-boost vaccination regimens using individual clones of recombinant FP9 or FPW in combination with recombinant modified V Ankara expressing the same antigen were evaluated for their ability to elicit T-cell responses against recombinant antigens from Plasmodium berghei (circumsporozoite protein) or human immunodeficiency virus type 1 (a Gag-Pol-Nef fusion protein). Gamma interferon enzyme-linked immunospot assay and fluorescence-activated cell sorting assays of the responses to specific epitopes confirmed the approximately twofold-greater cellular immunogenicity of FP9 compared to FPW, when given as the priming or boosting immunization. Equality of transgene expression in mouse cells infected with the two strains in vitro was verified by Western blotting. Directed partial sequence analysis and PCR analysis of FPW and comparison to available whole-genome sequences revealed that many loci that are mutated in the highly attenuated and culture-adapted FP9 strain are wild type in FPW, including the seven multikilobase deletions. These "passage-specific" alterations are hypothesized to be involved in determining the immunogenicity of fowlpox virus as a recombinant vaccine vector.

译文

:F的FP9菌株已被描述为比韦伯斯特FPV-M(FPW)菌株更具免疫原性的重组疫苗载体(R.J.Anderson等人,J.Immunol.172:3094-3100,2004)。这项研究扩大了比较范围,使其包括两个单独的重组抗原和源自两个菌株的多个而不是单个独立的病毒克隆。使用重组FP9或FPW的单个克隆与表达相同抗原的重组修饰的V Ankara组合的双痘病毒异源初免-加强疫苗接种方案,评估了它们针对伯氏疟原虫(环子孢子蛋白)或人类1型免疫缺陷病毒(一种Gag-Pol-Nef融合蛋白)。 γ干扰素酶联免疫斑点测定和针对特定表位的荧光激活细胞分选测定证实,FP9与FPW相比具有更大的两倍的细胞免疫原性,作为初次免疫或加强免疫。通过Western印迹验证了在体外感染这两种毒株的小鼠细胞中转基因表达的均等性。 FPW的定向部分序列分析和PCR分析以及与可用的全基因组序列的比较显示,在高度减毒和培养适应性FP9菌株中突变的许多基因座是FPW中的野生型,包括七个多碱基缺失。假设这些“通道特异性”改变涉及确定禽痘病毒作为重组疫苗载体的免疫原性。

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