How a ChAdOx based vaccine works
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.
Vaccitech’s heterologous prime-boost regimen involves two different vectors, ChAdOx and MVA, that encode the same antigens.
A first immunisation with ChAdOx potently primes T cells against the target antigen. A second immunisation with MVA boosts and expands the T cell response against the target antigen.
This approach reproducibly achieves immune responses that are differentiated by their high magnitude, high quality, and highly durable antigen-specific CD4+ helper and CD8+ cytotoxic T cells. These characteristics are ideal for T cell-based immunotherapies designed to treat infectious disease and cancer.