Vaccination with an Adenoviral Vector That Encodes and Displays a Retroviral Antigen Induces Improved Neutralizing Antibody and CD4+ T-Cell Responses and Confers Enhanced Protection
Vaccination with an Adenoviral Vector That Encodes and Displays a Retroviral Antigen Induces Improved Neutralizing Antibody and CD4+ T-Cell Responses and Confers Enhanced Protection
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DOI：
10.1128/jvi.01840-09
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发表时间：
2010-02-15
影响因子：
5.4
通讯作者：
Wildner, Oliver
中科院分区：
文献类型：
--
作者：
Bayer, Wibke;Tenbusch, Matthias;Wildner, Oliver
我们提出了一种新型的腺病毒载体，既编码和展示衣壳上的疫苗抗原，从而结合本身的基因为基础的和蛋白质疫苗接种，这种载体导致在朋友病毒（FV）模型中的疫苗接种结果得到改善。为了在腺病毒衣壳上呈递Friend鼠白血病病毒的包膜蛋白gp 70，将gp 70融合到腺病毒衣壳蛋白IX上。与使用传统的编码FV Env和Gag的腺病毒载体进行疫苗接种相比，使用编码和展示pIX-gp 70的腺病毒载体与编码FV Gag的载体组合进行疫苗接种，可显着改善对全身性FV攻击感染的保护作用，并高度控制血浆和脾脏中的病毒载量。这种改善的保护与改善的中和抗体滴度和更强的CD 4 + T细胞应答相关。使用展示gp 70而不编码它的载体，我们发现，虽然单独在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要的。这种基于腺病毒的新型疫苗可能是一种有价值的疫苗接种工具。
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.