Clinical assessment of a novel recombinant simian adenovirus ChAdOx1 as a vectored vaccine expressing conserved Influenza A antigens.

Clinical assessment of a novel recombinant simian adenovirus ChAdOx1 as a vectored vaccine expressing conserved Influenza A antigens.
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DOI:
10.1038/mt.2013.284
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发表时间:
2014-03
期刊:
Molecular therapy : the journal of the American Society of Gene Therapy
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腺病毒是诱导和增强对编码重组抗原的细胞免疫的有效载体。然而,普遍存在的针对常见人腺病毒血清型的中和抗体限制了它们的使用。猿腺病毒不会有同样的缺点。我们构建了一种复制缺陷的黑猩猩腺病毒载体疫苗,表达了保守的流感抗原、核蛋白(NP)和基质蛋白1(M1)。在这里,我们报告了这种新型重组猿腺病毒ChAdOx1 NP+M1接种后的安全性和T细胞免疫原性,这是首次采用3+3研究设计进行的人类剂量递增研究,随后在一些志愿者中增强了表达相同抗原的改良痘苗病毒Ankara。我们证明ChAdOx1 NP+M1是安全的和免疫原性的。ChAdOx1是一种很有前途的疫苗载体,可以用来运送疫苗抗原,在需要强大的细胞免疫反应来保护的地方。
Adenoviruses are potent vectors for inducing and boosting cellular immunity to encoded recombinant antigens. However, the widespread seroprevalence of neutralizing antibodies to common human adenovirus serotypes limits their use. Simian adenoviruses do not suffer from the same drawbacks. We have constructed a replication-deficient chimpanzee adenovirus-vectored vaccine expressing the conserved influenza antigens, nucleoprotein (NP), and matrix protein 1 (M1). Here, we report safety and T-cell immunogenicity following vaccination with this novel recombinant simian adenovirus, ChAdOx1 NP+M1, in a first in human dose-escalation study using a 3+3 study design, followed by boosting with modified vaccinia virus Ankara expressing the same antigens in some volunteers. We demonstrate ChAdOx1 NP+M1 to be safe and immunogenic. ChAdOx1 is a promising vaccine vector that could be used to deliver vaccine antigens where strong cellular immune responses are required for protection.
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