Viral Vector Platforms
How a ChAdOx vector platform works – in detail
![Vaccitech_MOA_Stage1](https://www.barinthusbio.com/storage/2021/08/Vaccitech_MOA_Stage1.png)
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.
![Vaccitech_MOA_Stage2](https://www.barinthusbio.com/storage/2021/08/Vaccitech_MOA_Stage2.png)
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.
![Vaccitech_MOA_Stage3](https://www.barinthusbio.com/storage/2021/08/Vaccitech_MOA_Stage3.png)
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.
![Vaccitech_MOA_Stage4](https://www.barinthusbio.com/storage/2021/08/Vaccitech_MOA_Stage4.png)
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 and HPV.
- ChAdOx1-MVA also induces high levels of CD4+ T cells, which allows for greater concentration of relevant antibodies.