Vaccitech Technology

The patented Vaccitech adenovirus vectors are known as chimpanzee adenovirus Oxford 1 and 2 (ChAdOx1 and ChAdOx2), and are in the group E simian adenovirus family, similar to the widely-studied chimpanzee adenovirus 63. These viruses have been engineered to be replication deficient and can be manufactured in well-established HEK293 cell lines containing the adenoviral E1 gene. The viruses have very high carrying capacity for the genes encoding cancer or pathogen antigens of interest. Vaccitech further optimizes and customizes the vectors through proprietary promoters and innovative insert design in its Early Development Lab. Both ChAdOx vectors have been moved into clinical studies, at the Jenner Institute, University of Oxford with hundreds of participants receiving the intramuscular ChAdOx1 vector as a prophylactic vaccine, or ChAdOx1/MVA prime-boost as a therapeutic regimen in trials for COVID-19, prostate cancer, MERS, malaria, tuberculosis, influenza and chikungunya virus. The platform has consistently been found to safely induce antibody, CD8+ and CD4+ immune responses, after a single dose. Vaccitech has been able to leverage this knowledge within its ChAdOx clinical programs that are in development and progressing rapidly.

Chimpanzee adenoviral vectors represent exceptional priming agents for disease-specific cellular and humoral immune responses, as is ideal for a single or two dose prophylactic vaccine. For therapeutic T cell responses, a single vector can be difficult to reuse in the first few months after administration due to transient anti-vector immunity. For this reason, we use a different vector to augment the levels of the induced, polyfunctional CD4+ and CD8+ T cells in therapeutic settings. MVA is an extremely effective boosting agent. Derived from the smallpox vaccine the virus was extensively cultured in avian cells to debilitate it from replicating in humans, while retaining its immunogenicity. It both boosts and prolongs polyfunctional CD4+ and CD8+ T cells induced by ChAdOx1 or ChAdOx2 and can be manufactured at scale using immortalized avian embryonic cell lines. The administration of two different vectors in this sequence as an immunotherapy is known as heterologous prime-boost.

Manufacturing

For both of these vectors the central issues of manufacturing have been overcome, a problematic area for novel cell-based therapies. Chimpanzee and MVA vectors have been manufactured at scales of hundreds of litres and administered to many thousands of clinical trial participants. Vaccitech has ongoing collaboration and manufacturing agreements with contract manufacturing organizations based in Europe, the United States and China.

Vaccitech has licensed the needed patents from Oxford University to advance all of the programs. Our ChAdOx1 vector patent is granted in the US and the EU.

References

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Morris, S.J., Sebastian, S., Spencer, A.J. and Gilbert, S.C., 2016. Simian adenoviruses as vaccine vectors. Future Virology, 11(9), pp.649-659.

Coughlan, L., 2020. Factors which contribute to the immunogenicity of non-replicating adenoviral vectored vaccines. Frontiers in Immunology, 11.

Ewer, K.J., Lambe, T., Rollier, C.S., Spencer, A.J., Hill, A.V. and Dorrell, L., 2016. Viral vectors as vaccine platforms: from immunogenicity to impact. Current opinion in immunology, 41, pp.47-54.

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Swadling, L., Capone, S., Antrobus, R.D., Brown, A., Richardson, R., Newell, E.W., Halliday, J., Kelly, C., Bowen, D., Fergusson, J. and Kurioka, A., 2014. A human vaccine strategy based on chimpanzee adenoviral and MVA vectors that primes, boosts, and sustains functional HCV-specific T cell memory. Science translational medicine, 6(261), pp.261ra153-261ra153.

Mayr, A. and Danner, K., 1979. Significance of animal pox for man following elimination of compulsory vaccination against smallpox. Berliner und Munchener tierarztliche Wochenschrift, 92(13), p.251.