phase I study of recombinant poxvirus Zika vaccines

自从人们认识到寨卡病毒是导致南美严重出生缺陷和神经紊乱的原因以来，迫切需要一种疫苗。我们将根据以前在人类中用于类似目的的两种病毒开发候选疫苗：改良的安卡拉牛痘病毒和禽痘病毒。在本研究中，我们将首先在实验室中使用这些疫苗保护小鼠免受寨卡病毒的侵害，从而证实这些疫苗在小鼠（停止/继续决策点）中起作用。然后，我们将使这些疫苗通过良好生产规范（GMP）生产过程（开发用于人的新产品所需的标准），并在人使用前进行最终安全测试。最后，我们将对这些疫苗进行首次人体试验（第一阶段临床试验），以检查它们的安全性，并且我们可以在人体内发现对疫苗的反应。我们的候选疫苗是基于已知对人类安全的病毒，并已多次用于制造其他疫苗。这些候选疫苗不同于目前正在开发的其他寨卡疫苗，因为它们既针对病毒的外部部分（包膜）产生抗体，也针对专门的白细胞反应（称为杀伤T细胞）。大多数疫苗的目标是只产生抗体反应。我们已经有成功的疫苗来对付由类似病毒引起的疾病，如黄热病和日本脑炎。这些疫苗既能产生抗体，也能产生杀伤T细胞反应。这种双轨方法旨在产生更好和更持久的免疫力。这对病毒家族（黄病毒）尤其重要，因为已知病毒之间存在交叉反应性问题。寨卡病毒疫苗将主要用于热带气候，那里有其他几种密切相关的病毒，如登革热、日本脑炎和黄热病（或者如果不是黄热病本身，那么大多数人应该已经接种过疫苗）。此外，我们预计基于改性安卡拉牛痘和鸡痘的疫苗在怀孕期间是安全的。选择这些痘病毒是因为它们的安全记录，它们在组合使用时已知的有益效果，以及它们在未来用作多种疾病疫苗的潜力。

Since the recognition of Zika virus as a cause of severe birth defects and nerve disorders in South America, a vaccine is urgently needed. We will develop vaccine candidates based on two viruses which have been used for similar puposes in humans before: modified vaccinia Ankara and fowlpox virus. In this research, we will first confirm that these vaccines work in mice (stop/go decision point) by using them to protect mice against Zika virus in the laboratory. We will then take these vaccines through the process of Good Manufacturing Practice (GMP) manufacture (the standard needed to develop a new product to use in people), and final safety testing vefore human use. Lastly, we will carry out the first tests of these vaccines in humans (phase I clinical trial) to check they are safe, and that we can detect a response to the vaccines in people.Our vaccine candidates are based on viruses which are known to be safe in humans and have been used many times to make other vaccines. These vaccine candidates are distinct from other Zika vaccines currently being developed because they aimed at both making antibodies against the outer part (envelope) of the virus, as well as specialised white blood cell responses (called killer T cells). Most vaccines aim to make only antibody responses. We already have successful vaccines to diseases caused by similar viruses, like yellow fever and Japanese encephalitis. These vaccines work both by creating antibodies, but they also make killer T cell responses. This twin-track approach is aimed at generating better and longer lasting immunity. This is especially important for the family of viruses (flaviviruses), where there are known problems with cross-reactivity between viruses. A Zika vaccine is going to be of most use in tropical climates, where there are several other closely related viruses found like dengue, Japanese encephalitis, and Yellow Fever (or if not Yellow Fever itself, then most people would already have had the vaccine). In addition, we expect vaccines based on modified vaccinia Ankara and Fowlpox to be safe in pregnancy. These poxviruses have been chosen for their safety record, their known beneficial effects when used in combination, and also their potential to be used as vaccines for more than one disease in the future.