L0015 A phase I study to determine the safety and immunogenicity of a Virus vaccine ChAdOx1 Chik in healthy adult volunteers Kate Harrison*1, Pedro Folegatti1, Fernando Ramos Lopez1, Mark W. Tilley1, Cesar Lopez-Camacho1, Young Chan Kim1, Lorena Preciado-Llanes1, Rachel Roberts1, Ian Poulton1, Alison Lawrie1, Katie Ewer1, Adrian Hill1, Arturo Reyes-Sandoval1

1 The , The University of Oxford, Oxford, United Kingdom Background: Chikungunya virus (CHIKV) is an emerging alphavirus, transmitted by Aedes mosquitoes. The acute disease is typically characterised by acute febrile illness, polyarthalgia and polyarthritis, which can last for months after infection. The WHO states that CHIKV has now been confirmed as endemic in over 60 countries, making the development of an effective vaccine paramount. We have developed ChAdOx1 Chik, a chimpanzee adenoviral vector expressing the structural cassette of CHIKV, able to induce neutralising in preclinical models. Materials/methods: ChAdOx1 Chik has now progressed to Phase I Clinical Trial at the University of Oxford. The vaccine is delivered as a single, un-adjuvanted intramuscular injection at three escalating doses. The primary endpoint is to assess the safety and tolerability of ChAdOx1Chik in healthy, adult volunteers for six months post vaccination. The secondary endpoint focuses on assessing cellular immunity, examined by IFN-γ ELISpot and intracellular cytokine staining in peripheral lymphocytes; and humoral immunity measured by ELISA against E2, the primary neutralising target Results: Preliminary safety data shows that ChAdOx1 Chik was well tolerated at all doses with no severe or serious adverse events reported to date. All local and systemic adverse events were self-limiting in nature and resolved within a week. Higher reactogenicity has been observed at the highest dose, but there were no safety concerns. To date, ex vivo IFN-γ ELISpot results indicate that the ChAdOx1 Chik vaccine is immunogenic even at the lowest dose, and significantly increases -specific T cell levels at day 14 and 28 post vaccination. Initial ELISA results show a significant increase in CHIKV specific IgG antibody production by 28 and 56 days post vaccination over pre-vaccination IgG levels. Conclusions: This is a first-in-human study of a Chikungunya vaccine based on a chimpanzee adenovirus expressing the CHIKV structural antigen. Preliminary results show that the vaccine is safe and well tolerated at all tested doses. A single dose of ChAdOx1 Chik is able to elicit both humoral and cellular responses significantly higher than baseline. The results of this trial will support a subsequent Phase Ib Clinical Trial of ChAdOx1 Chik to be held in an endemic area.

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