Phase Ib trial of a simple, multivalent vaccine to prevent Zika and Chikungunya

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The aim of this project is to complete a Phase Ib trial of a new bivalent vaccine to induce simultaneous immunity against Zika and Chikungunya, simplifying future vaccination campaigns for countries where both diseases co-circulate in the same regions, and where protection against both diseases is needed. Infection by ZIKV is a major concern worldwide due to the neurologic conditions, such as Guillain-Barré syndrome and a concurrent 20-fold increase in the incidence of microcephaly during the ZIKV outbreak in Brazil between 2014 and 2015 and in Mexico, where microcephaly caused by ZIKV has been confirmed. Aedes mosquitoes transmit Chikungunya virus (CHIKV), ZIKV and Dengue in the same geographical regions. CHIKV produces symptomatic disease in approximately ¾ of infected people, leading in many cases to long-term sequelae in people of all ages. Persistent arthritis cause disability for several years, contributing to poverty as young adults are unable to perform their physical activities required for work. Costs for families and governments are augmented due to the need to administer anti-inflammatory drugs to provide a short-term relief in patients. No vaccine is yet licensed for the prevention of CHIKV or ZIKV infections.The sudden presence of Zika and Chikungunya in the same geographical regions have overwhelmed health systems that were already challenged by Dengue, thus increasing the failure to provide treatment and preventive measures to their populations during the outbreak, while posing new challenges for treatment of both Zika and Chikungunya due to the long-term sequelae of more than 6 years for these diseases. These diseases are transitioning from an epidemic nature towards endemic diseases due to enabling drivers such as poor socioeconomic conditions, climate change and migration. A major breakthrough will be to provide governments with tools to simultaneously fight these highly prevalent arbovirus diseases and a multivalent vaccine able to protect against both Zika and Chikungunya would be an ideal preventive solution. This proposal has five major aims:1. Production of a large GMP batch of ChAdOx1-Zika (A parallel proposal submitted to Innovate UK could support alarge GMP batch of a ChAdOx1-Chikungunya vaccine).2. A Phase Ib trial of the bivalent vaccine in Mexico, in the city of Veracruz, where both diseases are prevalent.3. A study to assess incidence of Zika and Chikungunya in the ZIKV and CHIKV-endemic regions of Veracruz andMichoacan, to inform future Phase IIb efficacy trials in Mexico.4. Capacity development in Veracruz, Mexico to perform clinical trials.5. Reproduction toxicology for the Zika vaccine to support their use in pregnant women. This will consist of an embryo-foetal, pre- and post-natal development studies in the mouse.This proposal is fully aligned with the Officiald Development Assistance (ODA) and focuses on the development of vaccines that are appropriate for use in low- and middle- income countries, such as Mexico where recent outbreaks of Chikungunya and Zika have taken place in 2015 and 2016, respectively, and where arboviral diseases are contributing to poverty.