Vaccines and T cell Immunotherapies 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.
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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 Vaccitech and the Jenner Institute, University of Oxford with thousands 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+ T cell 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 weeks after administration due to transient anti-vector immunity. For this reason, we use a different vector to augment the levels of the CD4+ and CD8+ T cells to treat a variety of diseases. 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 adenoviral 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.
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