SynCon™ DNA Vaccine Platform
Modern vaccine design faces many challenges to overcome the limitations of conventional vaccines. To tackle complex infectious diseases, next-generation vaccines must have cross-strain applicability to address genetic evolution that is typical with pathogens such as influenza and HIV. Furthermore, to take the benefits of vaccines to a new level, the next generation of vaccines must not only prevent infections but be able to kill infected or mutated cells by inducing a T-cell immune response. This may enable such vaccines to tackle HIV and hepatitis C virus (HCV), as well as cancers. The solution to providing these and other benefits potentially lies with the capability to design sophisticated DNA-based vaccines.
The promise of DNA vaccines lies in the ability to design vaccines for the specific type of antibody and T-cell immune responses that are desired. As scientists' understanding of the immune system advances, the ability to design better-targeted DNA vaccines also grows.
Inovio's DNA vaccines are designed to generate the necessary T-cell response. But Inovio's vaccine design process reaches further. Employing bioinformatics, combining extensive genetic data, sophisticated algorithms, and ultra-powerful computing, Inovio's design process is able to synthetically define antigens and gene sequences common across different viral sub-types or taxonomic groups (families) of HIV, HCV, human papillomavirus (HPV), and influenza. By synthetically deriving consensus genes that look similar to a diverse panel of viral antigens, Inovio's SynConTM DNA vaccine constructs may provide a solution to the genetic "shift" and "drift" that is typical of these infectious diseases and be able to fight unmatched strains of a virus. SynConTM immunogens are able to elicit broad, diverse immune responses, which in theory are important to project against variable pathogens such as influenza, HCV and possibly HIV.
More technically speaking, SynCon™ DNA vaccine antigens are designed by aligning numerous primary sequences and choosing DNA-based triplets for the most common amino acid at each site. These antigens are further optimized for codon usage, improved mRNA stability, and enhanced leader sequences for ribosome loading. The DNA inserts are therefore optimized at the genetic level to give them high expression capability in human cells.
These design capabilities to better target appropriate immune system mechanisms and produce a higher level of the coded antigen enhance the overall ability of the DNA vaccine to induce the desired immune response.
Pre-clinical studies have shown that immunization of mice and non-human primates using SynCon™ DNA vaccine constructs elicited an immune response against multiple sub-types of the HIV, HCV, HPV, or influenza viruses. Vaccine candidates for all these diseases are being advanced through preclinical and clinical studies.
These candidates are being delivered into cells of the body using Inovio's highly efficient, proprietary electroporation DNA delivery technology. Efficient delivery of DNA vaccines in humans has been thought to be the short-coming of earlier generations of DNA vaccines.
The combination of SynCon™ DNA vaccine constructs and proprietary electroporation delivery technology results in the safety of a non-live, non-replicating vaccine with the stronger immune-stimulating power of live, replicating viral vectors.
The following charts display examples of exceptional preclinical antibody and T-cell data generated by SynConTM DNA vaccine constructs in animal models.
Inovio also has access to extensive manufacturing capabilities, including a state of the art cGMP DNA plasmid manufacturing facility, for internal development uses and contract manufacturing.
The combination of proprietary DNA vaccines, delivery technology development, and manufacturing capabilities creates a unique position for Inovio relative to peers with DNA vaccines and therapeutics programs.