A phase I clinical trial of a Chikungunya vaccine using a single dose and no adjuvant

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The aim of this proposal is to progress a novel Chikungunya vaccine to a phase I clinical trial. Chikungunya virus (CHIKV) infections are characterised by severe joint pain and fever during the acute phase and long-lasting debilitating arthralgia during the chronic phase. Aedes mosquitoes, the vectors transmitting CHIKV have undergone a dramatic expansion, causing CHIKV to become a global threat leading to long-term economic impacts in endemic countries. Development of an efficacious CHIKV vaccine is an achievable goal partly due to the low antigenic variability of the virus. An ideal vaccine should be safe, cheap, highly immunogenic, adjuvant-free and able to induce long-lasting immunity after a single dose. No vaccine is yet available for the prevention of CHIKV infection. Of approximately 23 experimental vaccines, only 2 are currently being tested in clinical trials. One vaccine consists of a virus-like particle that presents antigens in a similar array to those of a virus but without replicating, stimulating immune responses better than a non-particulate protein. However, this approach requires multiple injections to induce seroconversion and reach high antibody titres, increasing the costs, making logistics more complex and limiting use in low-income countries. Another approach consists on a recombinant live attenuated measles virus (MV) expressing surface CHIKV antigens. The vaccine has been shown to be immunogenic and safe in humans but it also requires two doses to induce good immune responses. The Jenner Institute has designed a new vaccine platform consisting on a chimpanzee adenoviral vector, ChAdOx2, which has already been manufactured to GMP and will enter clinical trials before the end of 2016. Chimpanzee adenoviruses are genetically stable, can be thermostabilised for ambient temperature storage and are suitable for use in all ages of the population. A similar simian adenoviral vector, ChAd3 expressing ebola antigens was shown to induce high titre neutralising antibody titres equivalent to those induced by the replication competent VSV-vectored Ebola vaccine that demonstrated 100% efficacy in a phase III trial. We are proposing to perform a phase I clinical trial to assess safety and immunogenicity of a single dose of a ChAdOx2 vaccine expressing chikungunya structural antigens: capsid and envelope glycoproteins. CHIKV structural antigens have been shown to stimulate the induction of protective antibodies. Our preliminaty results indicate that our CHIKV viral vectored vaccine is highly immunogenic in pre-clinical models and is able to stimulate high titres of neutralising antibodies after a single dose, similar to titres induced in infected people.