Viral Vector Platforms
How a ChAdOx vector platform works – in detail
1. ChAdOx and antigen design
Our ChAdOx vector platform is a modified version of an adenovirus isolated from a chimpanzee.
We insert precise genetic instructions for making one or more antigens, proteins specific to a pathogen or cancer, into the ChAdOx vector.
ChAdOx vector particles are formulated into a vaccine or immunotherapy to deliver the genetic blueprints for the antigen into cells of the body, to induce a robust immune response against the targeted disease.
2. ChAdOx expresses the antigens but cannot make copies of itself
ChAdOx’s natural biological ability to stimulate multiple immune pathways makes it an ideal delivery system for inducing targeted, long-lived immune responses.
- After injection of the vaccine or immunotherapy, ChAdOx binds to the surface of cells at the site of injection.
- ChAdOx enters the cell and uses the cell’s own protein production machinery to generate many thousands of copies of the antigens.
- The antigens are processed by the cells into proteins and peptides, which induce immune responses involving B cells and T cells.
3. CD4+ helper T cells and CD8+ cytotoxic T cells are activated upon recognition of antigenic peptides
T cells are a key component of effective immune responses against pathogens and cancer. CD8+ cytotoxic T cells are classically activated when presented with antigenic peptides associated with MHC class I molecules. CD4+ helper T cells activate when presented with antigenic peptides associated with MHC class II molecules.
4. Activated CD8+ cytotoxic T cells control and eliminate diseased cells such as virally infected cells or tumor cells
When activated CD8+ cytotoxic T cells encounter diseased cells with their cognate MHC class I associated antigenic peptide displayed on the cell surface, the CD8+ cytotoxic T cells identify the diseased cells and release molecules to selectively eliminate them.
ChAdOx is one of only a few immunotherapy and vaccine technologies that induces high levels of CD8+ cytotoxic T cells in addition to CD4+ T cells.
How MVA works
- MVA has a large antigen-carrying capacity and is especially immunogenic when used as a second dose in a sequential combination regimen.
- MVA is replication-deficient and has been administered in commercial use and in multiple clinical trials to over 130,000 people without significant safety issues, including 120,000 who received it in Germany as a next generation smallpox vaccine. An MVA vaccine (JYNNEOS) is being stockpiled by the U.S. government in preparedness for potential future smallpox and monkeypox outbreaks.
- The combination of an initial ChAdOx dose with an MVA follow up has consistently generated significantly higher magnitudes of CD8+ T cells as compared to other technologies and approaches. The induction of high levels of CD8+ T cells can play an important role in immune-system-led clearance of chronic and novel infections, such as in HBV.
- ChAdOx1-MVA also induces high levels of CD4+ T cells, which allows for greater concentration of relevant antibodies.