Rapid Cloning of Novel Rhesus Adenoviral Vaccine Vectors.
Rapid Cloning of Novel Rhesus Adenoviral Vaccine Vectors.
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DOI：
10.1128/jvi.01924-17
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发表时间：
2018-03-15
影响因子：
5.4
通讯作者：
Barouch DH
中科院分区：
文献类型：
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作者：
Abbink P;Kirilova M;Boyd M;Mercado N;Li Z;Nityanandam R;Nanayakkara O;Peterson R;Larocca RA;Aid M;Tartaglia L;Mutetwa T;Blass E;Jetton D;Maxfield LF;Borducchi EN;Badamchi-Zadeh A;Handley S;Zhao G;Virgin HW;Havenga MJ;Barouch DH
人类和黑猩猩腺病毒载体正在开发中，以规避现有的针对常见腺病毒载体（例如 Ad5）的抗体。然而，人类群体中仍然存在对这些载体的基线免疫力。传统克隆新型腺病毒疫苗载体是一个漫长而繁琐的过程，需要2个月或更长时间，并且需要罕见的独特限制性酶切位点。在这里，我们描述了一种新颖的、不依赖限制性内切酶的方法，用于快速克隆新的腺病毒疫苗载体，将总克隆过程缩短至 1 周。我们从恒河猴中开发了 14 种新型腺病毒载体，这些载体可以生长至高滴度，并且在小鼠中具有免疫原性。所有载体均与不寻常的腺病毒 G 类分组，并在人类中表现出极低的血清阳性率。新型腺病毒载体的快速克隆是开发新型载体平台的一种有前途的方法。恒河猴腺病毒载体可能对临床开发有用。重要性 为了克服对人类和黑猩猩腺病毒载体的基线免疫，我们开发了 14 种来自恒河猴的新型腺病毒载体。这些载体在小鼠中具有免疫原性，在人类中表现出极低的血清阳性率。恒河猴腺病毒载体可能对临床开发有用。
Human and chimpanzee adenovirus vectors are being developed to circumvent preexisting antibodies against common adenovirus vectors such as Ad5. However, baseline immunity to these vectors still exists in human populations. Traditional cloning of new adenovirus vaccine vectors is a long and cumbersome process that takes 2 months or more and that requires rare unique restriction enzyme sites. Here we describe a novel, restriction enzyme-independent method for rapid cloning of new adenovirus vaccine vectors that reduces the total cloning procedure to 1 week. We developed 14 novel adenovirus vectors from rhesus monkeys that can be grown to high titers and that are immunogenic in mice. All vectors grouped with the unusual adenovirus species G and show extremely low seroprevalence in humans. Rapid cloning of novel adenovirus vectors is a promising approach for the development of new vector platforms. Rhesus adenovirus vectors may prove useful for clinical development. IMPORTANCE To overcome baseline immunity to human and chimpanzee adenovirus vectors, we developed 14 novel adenovirus vectors from rhesus monkeys. These vectors are immunogenic in mice and show extremely low seroprevalence in humans. Rhesus adenovirus vectors may prove useful for clinical development.