|
VGX Pharmaceuticals is developing a new generation of DNA Vaccines which utilize synthetic consensus sequences and antigens for key HIV, HCV, HPV, and influenza proteins that offer coverage across different viral sub-types or taxonomic groups. SynCon™ immunogens include several molecular features aimed at improving the immune potential of the inserted genes. These genes are not derived from actual viruses rather they are designed bioinformatically to look similar to a diverse panel of viral antigens. This allows them to elicit immune responses that are much more broad and induce more diverse immune responses, which in theory are important to project against variable pathogens such as influenza, HCV and possibly HIV. The inserts are optimized at the genetic level to give them high expression capability in human cells. When these features are combined with the highly efficient delivery of the electroporation technology we wind up with inserts that are as safe as non live non replicating vaccines, but have the stronger immune stimulating power of live replicating vectors. Pre-clinical studies have shown that immunization of mice and non-human primates using SynCon™ DNA vaccine constructs for each virus elicits an immune response against multiple sub-types of the HIV, HCV, HPV, or influenza viruses. VGX is also developing its proprietary CELLECTRA™ DNA Delivery Device as a novel adaptive electroporation device to deliver its DNA vaccine candidates. VGX Pharmaceuticals’ SynCon™ DNA vaccine antigens are designed by aligning numerous primary sequences and choosing the most common amino acid or base pair at each site by using high-powered and patented approaches. VGX has developed consensus sequences and antigens for key human immunodeficiency virus (HIV), hepatitis C virus, human papilloma virus, and influenza proteins that offer coverage across different viral sub-types and taxonomic groups. These antigens are further optimized for codon usage, for improved mRNA stability, and for enhanced leader sequence for ribosome loading. VGX’s prolific research pipeline of next-generation DNA vaccines and therapeutics includes candidates for HIV, HPV, Influenza, HCV, and human Growth Hormone Releasing Hormone (hGHRH). These candidates will be delivered by VGX’s proprietary DNA delivery system (CELLECTRA™ electroporation) which enhances delivery on DNA vaccines. Efficient delivery of DNA vaccines in humans has been thought to be the short-coming of the previous generation of DNA vaccines. VGX also has extensive manufacturing capabilities, including a state of the art cGMP facility for DNA plasmid manufacturing for internal development uses as well as for contract manufacturing. The combination of proprietary DNA content, delivery system, and manufacturing capabilities creates a unique position for VGX relative to its peers with DNA vaccines and therapeutics programs. PROOF OF CONCEPT STUDIES AND PRE-CLINICAL DATA IN ANIMAL MODELS 1. Melanoma: Mouse Model Direct injection of Vpr DNA (VGX-150) into melanoma eradicates tumors in mice
2. GHRH: Canine Model
3. Avian Influenza: Mouse Challenge
4. HIV: Macaque Model
|
|||||||||||||||||||||||||||||||||||||||||||||||||
Ref:
Mol. Therapy 2006
DNA-based vaccines and therapeutics deliver the immunogen or the therapeutic protein in the form of plasmid DNA encoding the protein of interest. The body then produces the protein of interest and elicits the appropriate immune logic response. Vaccination with DNA has multiple potential advantages over the present technology used for vaccination against a variety of infectious diseases. DNA vaccines are easier to manufacture, can be stored at room temperature, and have less safety concerns when delivered to the patient. Furthermore, DNA vaccine antigens can be combined more readily than those of more traditional vaccine approaches.
Over the last two decades, DNA vaccines have become a potent means of providing immune responses or protective immunity against viruses, bacteria and parasites in many species from fish to primates, including humans. DNA vaccines, comprising plasmid DNA encoding proteins from pathogens, allergens, and tumors, are being evaluated as prophylactic vaccines and therapeutic treatments for infectious diseases, allergies and cancer. The use of DNA as a means of vaccination offers potential benefits in protective efficacy, cross-strain applicability, development speed and manufacturing cost compared with conventional vaccines. DNA vaccines are known to be particularly effective in inducing killer T-cell responses which are an important ingredient in fighting infections.
The principals of VGX Pharmaceuticals have a long standing history in this growing field. VGX’s Cofounder Professor David B. Weiner has been one of the most important pioneers in the field of DNA vaccines. His original DNA vaccines research and patents in the early 1990’s became the basis for private biotechnology company Apollon Inc., which subsequently became a part of Wyeth Vaccines. Dr. Weiner's DNA vaccines targeting HIV were the first candidates to make it into clinical testing. Dr. J. Joseph Kim, Cofounder and CEO of VGX has been an expert in DNA vaccines since the mid-1990’s. Dr. Kim’s extensively published area of research was the improvement of immune responses to DNA vaccines by utilizing various molecular adjuvants. Drs. Kim and Weiner collaborated on over 70 biomedical research publications in major academic journals. Moreover, VGX’s Chief Medical Officer, Dr. C. Jo White, assisted in writing and filing the first IND for Merck’s influenza DNA vaccine candidates in 1995.
With such strong internal capabilities, VGX Pharmaceuticals has chosen DNA vaccines as a new area of research to complement and expand our current product development programs in infectious diseases and cancer. In February of 2007, VGX Pharmaceuticals purchased a Texas-based DNA vaccines company ADViSYS Inc. with a cGMP manufacturing facility to produce DNA plasmids for injection and a novel electroporation device (CELLECTRA™ electroporation) for delivery. In addition, the Company licensed from Baylor College of Medicine the rights to human health applications of GHRH-based therapies and new plasmids and plasmid components. VGX also in-licensed the new generation of improved DNA vaccines program from Professor Weiner’s lab at the University of Pennsylvania in April of 2007. As a result, VGX Pharmaceuticals was able to rapidly launch a fully-integrated DNA vaccines franchise with state of the art capabilities.