The EpiVax Approach to Vaccine Design and Vaccine Redesign
EpiVax identifies T-cell epitopes, short peptide sequences displayed by antigen presenting cells to T cells, to create immunogenic and protective vaccines from whole genomes. Identifying epitopes and designing the vaccines are done in-silico, using proprietary computer algorithms assembling into a web-based platform called iVAX.
Why design concatameric epitope-based vaccines?
Epitope-driven vaccines offer distinct advantages over traditional subunit vaccines. Multiple epitopes derived from more than one antigen can be packaged together. In this way, a broad-based immune response directed against multiple antigenic proteins associated with the pathogen can be elicited without the need to manufacture and administer large quantities of protein, much of which will be immunologically irrelevant or potentially even self-reactive (could cause autoimmune diseases). This is likely to reduce formulation challenges, cost, and safety risk. The use of epitopes also helps to mitigate safety concerns stemming from the use of intact recombinant proteins that may have undesired biological activity (enzymes, immunomodulators, cross-reactivity, toxins, etc).
The EpiVax Approach
Four major steps comprise the EpiVax strategy:
- Genomes are mined using computational tools to identify genes that encode proteins with promising vaccine antigen properties such as secretion, up-regulated expression, immunogenicity and virulence.
- Immunoinformatics tools are then used to map protein sequences for short, linear putative T-cell epitopes.
- Sequences are synthesized as peptides and evaluated for human leukocyte antigen (HLA) binding and antigenicity in survivors of infection or vaccinees.
- Prototype epitope-based vaccines are evaluated for immunogenicity and efficacy in humanized mice.
A genomes-to-vaccine strategy for rational vaccine design rests on two premises:
- A minimal set of immunogens that induces a robust and sustained immune response to a pathogen can be discovered using high throughput methods.
- Administration of these immunogens, in a suitable delivery vehicle together with adjuvant, will protect against infection or disease.