Rabies remains an important cause of death, fear, and economic disruption in many regions of the world. Around 1.5 million people are treated for exposure each year, and approximately 59 000 die. Around 95% of human cases occur in Asia and Africa, mostly affecting children in poor rural communities.
Currently approved human vaccines require several doses to be effective and are too expensive for mass vaccination programmes in rabies endemic regions. They are instead used as pre-exposure prophylaxis in some high-risk groups, and as part of post-exposure prophylaxis alongside anti-rabies immunoglobulin. The majority of post-exposure treatment cost are borne by patients and their families in poor communities.
Exposure to rabies is most commonly through being bitten by an infected animal, usually a dog. Given the high costs of human vaccines, control of rabies is currently most economically viable through the vaccination and control of dog populations. Such control has become a focus of WHO-led eradication efforts. The high turnover and mobility of dog populations in many areas makes such control difficult to achieve, and even more difficult to sustain in the long term.
A cheap, easy to use rabies vaccine for humans that could be used in mass vaccination campaigns would be a valuable weapon in the battle against rabies. Vaccine effectiveness after a single dose, ease and cost of manufacture, plus minimising reliance on cold-chain storage are all important factors in the potential impact and new vaccine in limiting the human and economic suffering caused by rabies.
We have developed a novel rabies vaccine based on an adenovirus vector – ChAdOx2 RabG. The vector is unable to replicate in mammalian cells, but results in a protective immune response against the rabies virus. The vector is based on a chimpanzee adenovirus strain, removing the risks associated with pre-existing immunity to the vector in humans.
In a non-human primate trial, this novel rabies vaccine outperformed a currently licenced vaccine: a single dose protected 100% of animals when exposed to rabies 22 months after vaccination.
Cost estimates suggest this vaccine could be produced for less than US$4 a dose at scale, making it significantly cheaper than current rabies vaccines and economical to use for large-scale pre-exposure prophylaxis.
From 2017 to 2019 we developed a new process for GMP manufacturing of ChAdOx2 RabG, and this was used to produce the vaccine for clinical trials at the Clinical Bio-Manufacturing Facility. The vaccine is now being used in a Phase I clinical trial in the UK (NCT04162600) and a Phase Ib/II clinical trial in Tanzania (NCT04270838). These trials are testing the safety of the vaccine, alongside analysing the strength and longevity of the protective immune response induced in a range of human populations.
The process used to manufacture ChAdOx2 RabG has been further developed by our team since 2019, and this work formed the basis of the process for manufacturing the Oxford-AstraZeneca COVID-19 vaccine (ChAdOx1 nCOV-19). It has also led to the establishment of the Bioprocess and Analytical Development (BiPAD) initiative, which aims to translate promising research in vaccines and molecular medicine to patient benefit more effectively.
We are also working on technologies to improve the stability of Adenovirus vectored vaccines at higher temperatures, including novel technologies such as sugar matrix thermostabilisation and improvements on currently available technologies such as liquid formulations and lyophilisation.