phase I study of recombinant poxvirus Zika vaccines

由于寨卡病毒被认为是南美洲严重出生缺陷和神经疾病的原因，因此迫切需要疫苗。我们将开发基于两种病毒的候选疫苗，这两种病毒以前在人类中用于类似目的：改良的安卡拉牛痘病毒和鸡痘病毒。在这项研究中，我们将首先通过在实验室中使用这些疫苗来保护小鼠免受寨卡病毒感染，从而确认这些疫苗在小鼠中起作用（停止/继续决策点）。然后，我们将这些疫苗通过良好生产规范（GMP）生产过程（开发用于人类的新产品所需的标准），并在人类使用之前进行最终安全测试。最后，我们将进行这些疫苗在人类身上的第一次测试（第一阶段临床试验），以检查它们是否安全，我们可以检测到人们对疫苗的反应。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。这些候选疫苗与目前正在开发的其他寨卡疫苗不同，因为它们旨在制造针对病毒外部（包膜）的抗体，以及专门的白色血细胞反应（称为杀伤T细胞）。大多数疫苗的目标是只产生抗体反应。我们已经有了成功的疫苗来预防由类似病毒引起的疾病，如黄热病和日本脑炎。这些疫苗通过产生抗体来发挥作用，但它们也会产生杀伤性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。这对于病毒家族（黄病毒）尤其重要，已知病毒之间存在交叉反应性问题。寨卡疫苗将在热带气候中使用最多，那里还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，那么大多数人已经接种了疫苗）。此外，我们预计基于改良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，它们在组合使用时的已知有益效果，以及它们在未来用作一种以上疾病的疫苗的潜力。

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.