Ruhr-University Bochum, Institute of Microbiology and Hygiene, Department of Molecular and Medical Virology, Universitaetsstr. 150, Bldg. MA, Rm. 6-40, D-44801 Bochum, Germany.
J Virol. 2010 Feb;84(4):1967-76. doi: 10.1128/JVI.01840-09. Epub 2009 Dec 9.
We present a new type of adenoviral vector that both encodes and displays a vaccine antigen on the capsid, thus combining in itself gene-based and protein vaccination; this vector resulted in an improved vaccination outcome in the Friend virus (FV) model. For presentation of the envelope protein gp70 of Friend murine leukemia virus on the adenoviral capsid, gp70 was fused to the adenovirus capsid protein IX. When compared to vaccination with conventional FV Env- and Gag-encoding adenoviral vectors, vaccination with the adenoviral vector that encodes and displays pIX-gp70 combined with an FV Gag-encoding vector resulted in significantly improved protection against systemic FV challenge infection, with highly controlled viral loads in plasma and spleen. This improved protection correlated with improved neutralizing antibody titers and stronger CD4(+) T-cell responses. Using a vector that displays gp70 without encoding it, we found that while the antigen display on the capsid alone was sufficient to induce high levels of binding antibodies, in vivo expression was necessary for the induction of neutralizing antibodies. This new type of adenovirus-based vaccine could be a valuable tool for vaccination.
我们提出了一种新型的腺病毒载体,它既能在衣壳上编码又能展示疫苗抗原,从而将基因疫苗和蛋白疫苗结合在一起;该载体在 Friend 病毒(FV)模型中产生了更好的免疫效果。为了在腺病毒衣壳上展示 Friend 鼠白血病病毒的包膜蛋白 gp70,我们将 gp70 融合到了腺病毒衣壳蛋白 IX 上。与用传统的 FV Env 和 Gag 编码腺病毒载体进行疫苗接种相比,用编码和展示 pIX-gp70 的腺病毒载体与编码 FV Gag 的载体联合进行疫苗接种,可显著提高对全身 FV 攻击感染的保护效果,血浆和脾脏中的病毒载量得到高度控制。这种更好的保护效果与更高的中和抗体滴度和更强的 CD4+ T 细胞反应相关。我们使用不编码 gp70 的载体发现,尽管衣壳上的抗原展示足以诱导高水平的结合抗体,但体内表达对于诱导中和抗体是必需的。这种新型的基于腺病毒的疫苗可能是一种有价值的疫苗工具。