Development and manufacture of an improved replication-deficient simian adenoviral vector to prevent COVID-19

The University of Oxford and Vaccitech jointly developed and then exclusively out-licensed a serogroup E chimpanzee adenoviral vector vaccine encoding the SARS-CoV-2 spike glycoprotein to AstraZeneca. This vaccine, ChAdOx1 nCoV-19, given as a single dose, has moved into Phase 2/3 studies in the UK, and in August 2020 begins Phase 3 studies in the US and Brazil. There are concerns that anti-vector immunity to the ChAdOx1 backbone may limit early boosting responses, or even boosts given on a yearly basis. Vaccitech has developed an alternative serogroup C chimeric gorilla adenoviral vector vaccine ("GAdVac"), which has been shown in completed murine studies to elicit higher antibody and T cell immune responses than the ChAdOx1 candidates. Vaccitech is now developing the full-length spike glycoprotein encoding GAdVac candidate and will use this as both a stand-alone vaccine and evaluate the use of this candidate as a prime and a boost for the ChAdOx1 platform. Efficacy studies in ferrets will be pursued with Public Health England at Porton Down. The pre-master virus seed will be produced in the SOP- controlled Early Development Laboratories at Vaccitech in Oxford, and then transferred to Advent (Rome, Italy) for GMP manufacture. Advent has successfully made three GMP released lots of ChAdOx1 vectors for Vaccitech. Scientific advice will be sought from MHRA, and a formal GLP toxicology study will be performed due to the novelty of this vector. Within 12 months, the CTA to begin a Phase 1 immunogenicity study will be complete.