Adenovirus-Based Vaccines: Comparison of Vectors from Three Species of Adenoviridae
Adenovirus-Based Vaccines: Comparison of Vectors from Three Species of Adenoviridae
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DOI：
10.1128/jvi.00450-10
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发表时间：
2010-10-01
影响因子：
5.4
通讯作者：
Ertl, H. C. J.
中科院分区：
文献类型：
--
作者：
Chen, H.;Xiang, Z. Q.;Ertl, H. C. J.
为了更好地了解腺病毒（Ad）作为人类疫苗研究载体的广泛适用性，我们比较了来自C家族的四种腺病毒（Ad）载体，（Ad人血清型5 [HAdV-5;这里称为AdHu 5]），D（HAdV-26;这里称为AdHu 26），和E（猿血清型SAdV-23和SAdV-24;这里称为黑猩猩血清型6和7 [分别为AdC 6和AdC 7]）。血清阳性率和中和抗体的两个人源性广告的滴度被发现高于以前的报告，特别是在撒哈拉以南非洲国家。相反，AdC 6和AdC 7的患病率和滴度明显较低。来自美国的健康成年人具有容易检测到的识别Ad病毒的循环T细胞，在一些个体中，其水平在对AdHu 26的响应中出乎意料地高。对AdHu 5的T细胞应答的幅度与对AdHu 26的T细胞应答的幅度相关，表明T细胞识别保守表位。在小鼠中，所有不同的Ad载体诱导的CD 8（+）T细胞应答在其幅度和细胞因子产生谱方面是相当的。比较Ad载体的不同组合的初免-加强方案未能表明顺序使用来自不同家族的Ad载体比使用来自相同家族的血清学上不同的Ad载体产生更高的免疫应答。此外，由AdHu 26和AdC载体诱导的转基因产物特异性抗体应答显著低于由AdHu 5载体诱导的那些。AdHu 26载体和AdC载体在较小程度上诱导更有效的Ad中和抗体应答。这些结果表明，AdHu 26作为疫苗载体的潜力可能受到与基于其他流行的人类Ad的载体所发现的那些类似的限制。
In order to better understand the broad applicability of adenovirus (Ad) as a vector for human vaccine studies, we compared four adenovirus (Ad) vectors from families C (Ad human serotype 5 [HAdV-5; here referred to as AdHu5]), D (HAdV-26; here referred to as AdHu26), and E (simian serotypes SAdV-23 and SAdV-24; here referred to as chimpanzee serotypes 6 and 7 [AdC6 and AdC7, respectively]) of the Adenoviridae. Seroprevalence rates and titers of neutralizing antibodies to the two human-origin Ads were found to be higher than those reported previously, especially in countries of sub-Saharan Africa. Conversely, prevalence rates and titers to AdC6 and AdC7 were markedly lower. Healthy human adults from the United States had readily detectable circulating T cells recognizing Ad viruses, the levels of which in some individuals were unexpectedly high in response to AdHu26. The magnitude of T-cell responses to AdHu5 correlated with those to AdHu26, suggesting T-cell recognition of conserved epitopes. In mice, all of the different Ad vectors induced CD8(+) T-cell responses that were comparable in their magnitudes and cytokine production profiles. Prime-boost regimens comparing different combinations of Ad vectors failed to indicate that the sequential use of Ad vectors from distinct families resulted in higher immune responses than the use of serologically distinct Ad vectors from the same family. Moreover, the transgene product-specific antibody responses induced by the AdHu26 and AdC vectors were markedly lower than those induced by the AdHu5 vector. AdHu26 vectors and, to a lesser extent, AdC vectors induced more potent Ad-neutralizing antibody responses. These results suggest that the potential of AdHu26 as a vaccine vector may suffer from limitations similar to those found for vectors based on other prevalent human Ads.