Clinical Stage multivalent vaccines against viral haemorrhagic fevers

Since the 2013-2016 Ebola virus (Zaire Ebolavirus/EBOZ) outbreak, there have been a number of other documented outbreaks of lethal haemorrhagic fever caused by filoviruses and arenaviruses. It is generally accepted that either a mixture of monovalent vaccines or, preferably, a multivalent vaccine, will be required to confer protective immunity against viral haemorrhagic fever. The costs of developing individual vaccines against filoviruses and an arenavirus (Lassa virus (LASV)) will be prohibitively high, and there is a risk that funding will not be found to develop individual vaccines, leaving the populations in low and middle income countries at risk. Our vaccine modality of choice, for vaccine manufacture, is a chimpanzee adenoviral vector (ChAdOx1). ChAds have been administered in clinical trials to over 6,500 vaccinees, across eight disease areas, with an excellent safety profile in adults, children and babies. Single dose regimens are highly immunogenic, generating humoral and cellular immunity. Importantly, these vaccines can be thermostabilised by a simple process, removing the need for a cold chain storage and greatly reducing delivery costs. Of note, the emergency response to Ebola led to large-scale manufacture of viral vectors and there is now an accumulated manufacturing experience for viral vectored vaccines at scale. To reduce the costs and increase the utility of vaccines against emerging pathogens, we took a stepwise and iterative approach, in our stream I funding, toward the design and testing of multivalent vaccines against key outbreak pathogens; filoviruses (EBOZ, SUDV, MARV) and LASV. By the end of our programme we had developed, tested and produced scalable, immunogenic, and protective multivalent viral vectored vaccines for deployment against Filoviruses and Lassa fever. We now aim to rapidly translate these promising preclinical vaccines into clinical trials. This is facilitated by the close ties to an in-house bio-manufacturing facility (CBF), an experienced team of personnel at the Centre for Clinical Vaccinology and Tropical Medicine (CCVTM), adept at progressing first-in-human clinical trials and collaborations in-situ in Africa to clinically assess candidate vaccines in relevant settings. We seek to build on this experience and progress our early pre-clinical work to clinical development and to test a multivalent viral vectored vaccine in a first-in-human Phase I clinical trial.