Outbreak Pathogens: New Chikungunya Virus Vaccine Programme
By Prof Arturo Reyes-Sandoval, Jenner Investigator
Chikungunya virus (CHIKV) is an emerging alphavirus that causes acute febrile illness and chronic, severe and debilitating arthralgias. Alphaviruses are enveloped, positive sense, single-stranded RNA viruses. They are usually referred to as either ‘Old World’ or ‘New World’ viruses, with Old World viruses generally associated with rheumatic disease in humans. The arthritogenic ‘Old World’ alphaviruses comprise CHIKV, Ross River virus (RRV), Barmah Forest virus (BFV) and o’nyong-nyong virus, amongst others.
Similarly to Zika virus, CHIKV is transmitted by Aedes mosquitoes, which are present in tropical and sub-tropical regions and have spread the virus through East Africa, the Indian Ocean Islands, South East Asia and the Americas.
The control of the mosquito has not been useful to contain the virus and new preventive strategies are needed. CHIKV causes large outbreaks, such as the one reported on Reunion Island, where approximately 255,000 cases were reported between 2005 and 2006, in a total population of 770,000. India has also been heavily affected by CHIKV, where more than 1.39 million cases of viral infection were reported in 210 districts of 13 states during 2006. In densely populated regions, it is estimated that the infection rate in humans is between 30% and 75%.
Severe disease by CHIKV can lead to chronic incapacitating arthralgia that may linger for weeks, months or years, occurring in a fluctuating manner. During the acute phase, the pain can be excruciating, involving joints from fingers, wrists, elbows, toes, ankles and knees and affected people adopt a characteristic stooped walking position that gave the name ‘Chikungunya’, meaning ‘to walk bent over’ in the Kimadonde language of Mozambique (Hoarau et al. J. Immunol. 2010). An efficacious vaccine could contribute to the prevention of CHIKV infection and to limit the spread to more regions around the world. Evidence indicates that a vaccine targeting the external structural antigens can elicit protective antibodies able to neutralise virus entry and protect susceptible animal models. The fact that CHIKV does not present high variability in these target antigens, indicates that a protective vaccine can be achieved.
The Jenner Institute research group led by Prof Arturo Reyes-Sandoval has developed a Chikungunya vaccine using recombinant chimpanzee adenoviruses and MVA expressing structural and non-structural antigens of this virus. The vaccine induces high frequencies of antigen-specific T cells and high titres of antibodies able to neutralise the virus using in vitro techniques. These results have been key to receive funding by Innovate UK for GMP development and a phase I clinical trial in Oxford, expected to take place in 2017.
The Chikungunya programme is one of three research grants awarded in June 2016 by Innovate UK to the group lead by Prof Arturo Reyes-Sandoval, which included two other grants for pre-clinical studies: one for a dengue macaque challenge and one for Zika virus vaccine development. Innovate UK is an executive non-departmental public body, sponsored by the UK Department for Business, Innovation & Skills.