Protective efficacy and neutralisation to select an optimal Zika virus vaccine

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Zika virus (ZIKV) is an emerging Flavivirus transmitted by Aedes mosquitoes that is now rapidly spreading throughout South, Central and North America. ZIKV is a major concern worldwide due to the neurologic conditions, such as Guillain-Barré syndrome in French Polynesia, and a concurrent 20-fold increase in the incidence of microcephaly during the ZIKV outbreak in Brazil between 2014 and 2015. Unfortunately, no vaccine to prevent infection is currently available. We have recently developed two new vaccine platforms suitable for human use, based on replication-deficient chimpanzee adenoviral vectors ChAdOx and Modified Vaccinia Ankara expressing various versions of Zika structural antigens. We have started evaluating the immunogenicity of our vaccine candidates using ELISA and cellular assays, such as ELISPOT. Here, we propose to extend those studies to use functional assays such as neutralisation of viruses and infection of pre-clinical models to select the optimal vaccine candidate for a clinical trial in the near future. Our proposal aims are: (1) Compare the protective efficacy of 10 novel vaccines produced at the Jenner Institute, using pre-clinical models suitable for infection with ZIKV at the Public Health England laboratories; (2) Measure the ability of vaccine-immune sera to neutralise ZIKV entry using in vitro cell cultures to establish quantitative neutralising antibody titres required for protection in mice; and (3) Identify antibody titres in samples from infected volunteers in Mexico to define titres induced during acute infection and convalescent period of the disease, and thus define titers of physiological relevance for a vaccine candidate. We will combine laboratory data with field data obtained from areas with prevalence of ZIKV infection, supported by infrastructure of Oxford NDM-Mexico collaborative laboratories, a network dedicated to the study of emerging infectious diseases. The information obtained at the end of this study will be key to inform vaccine development and confirm the most immunogenic and protective ZIKV vaccine candidate that would be suitable for a clinical trial. This project will also strengthen new synergistic links between the PHE (https://www.gov.uk/government/organisations/public-health-england), Oxford Biochemistry Department (http://www.bioch.ox.ac.uk), Oxford Vaccine Group (http://www.ovg.ox.ac.uk), Oxford NDM-Mexico network for emerging pathogens (http://www.ndm.ox.ac.uk/mexico/home) and the Jenner Institute (http://www.jenner.ac.uk/home) that will be invaluable for the UK capability to respond rapidly to emerging infections.