phase I study of recombinant poxvirus Zika vaccines

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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.