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

A leading candidate vaccine for COVID-19 is the chimpanzee adenoviral vector known as ChAdOx1 nCoV-19, which has been jointly developed and then exclusively licensed by the University of Oxford and Vaccitech to AstraZeneca. The vaccine is being evaluated in over 11,000 participants in the UK primarily as a single immunisation and in August will begin a 30,000-person Phase 3 study in the United States. There are concerns that this candidate vaccine may require a second dose, and may even be needed on a yearly basis, and that immune responses to the vector itself may limit the effectiveness of ChAdOx1 nCoV-19 over time. Vaccitech has developed a more immunogenic gorilla adenoviral vector with potential to have less vector cross-reactivity, induce stronger immune responses (both antibodies and T cells), and overcome some of the present concerns with ChAdOx1 nCoV-19. In this proposal all pre-clinical work will be completed to be ready to file a regulatory application to begin the initial Phase 1 clinical study. This preparation includes animal studies, clinical trial lot manufacture, formal toxicology studies, and any necessary regulatory interactions.

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.