ChronVac-C®
ChronVac-C® is what is termed a therapeutic vaccine, i.e. a vaccine given to people already infected with Hepatitis C, with the intention of reinforcing their immune response. ChronVac-C® is also what is termed a ‘genetic vaccine', which means that rather than just filling syringes with the vaccine, the vaccine's genetic code, its DNA, is used. When the vaccine DNA is injected into muscle, it is absorbed by muscle cells, which then convert the DNA into protein, and produce the vaccine to activate the body's immune response themselves.
One big problem with this type of DNA vaccination is that if ordinary syringes are used, most of the DNA remains outside muscle cells and is metabolised. However, DNA vaccine enjoys many benefits: it is easy and cheap to produce, has a long shelf-life, and the same production facility can be used for a wide array of vaccines.
But to exploit these advantages it is necessary to resolve the first and biggest problem-muscle cells do not take up the vaccine DNA. HCV infections in the liver do not trigger an immune response very effectively, which may be a contributor to the high proportion of chronic carriers. In other words, activating the immune response to a non-mutable portion of HCV elsewhere in the body rather than the liver may prove very valuable. Muscle is a good location, and where vaccinations are usually administered.
Tripep has identified a solution to these problems through its collaboration with US corporation Inovio, a world leader in in vivo electroporation. This technology, implemented with Inovio's Medpulser® DNA Delivery System (DDS), involves exposing cells to short-duration electric pulses, which produce temporary pores in the cell membrane. When the pores open DNA can enter the cell. The pores then quickly re-seal.
Inovio has now developed this technology so it can be applied to humans. Firstly, the physician injects ChronVac-C® into a muscle, and immediately applies the Medpulser® DDS and introduces its four electrodes to the same region as the vaccine DNA was injected. A few short-duration electrical pulses are then applied, and treatment is finished. Complete therapy would encompass four similar treatments, once a month. Hopefully, this would result in the body activating an immune response that helps heal the infection.
ChronVac-C® has been in development since 1999. Tripep has been able to produce models to demonstrate what the vaccine can do. ChronVac-C® can activate B cells and T cells, the latter currently regarded as the most significant to clearing the chronic infection. Experiments on mice have demonstrated that ChronVac-C® vaccination activates T cells that enter the liver and eliminate the liver cells producing HCV protein, a basic prerequisite for any therapeutic vaccine to work. The combination of ChronVac-C® and Medpulser® DDS was noted at the Second Hepatitis C Conference in Dublin on 23 June 2006, when Professor Matti Sällberg presented positive results from mouse experiments, which were then followed by more positive results in the year. The company was able to demonstrate that the combination triggered a T cell response, that was able to enter the liver and eliminate HCV protein-producing liver cells. This is genuine proof of concept for the combination of ChronVac-C® and Medpulser® DDS, and exactly the desired result of a therapeutic vaccine.
2006, a Momentous Year for ChronVac-C®
ChronVac-C® made several breakthroughs in 2006, and the project achieved several milestones. In January, the company was able to report that it had entered a collaboration agreement with San Diego-based company Inovio on the joint clinical development of ChronVac-C®. This agreement provides Inovio with part-ownership of ChronVac-C®, while in return, Tripep secures access to Inovio's human DNA vaccination technology. GMPproduced ChronVac-C® was delivered from Vecura AB in February, and two Medpulser® DDS in vivo electroporation devices were supplied to the company. This meant that the toxicological evaluation of ChronVac-C® could start immediately. In March, the company secured its most important patent on ChronVac-C® until that time, which protected the heavily modified and enhanced hepatitis C virus gene that ChronVac-C® contains. This means that Tripep has protection on its CD, ChronVac- C®, for at least 17 years. Three toxicology studies are now being conducted, one for biodistribution and pharmacokinetics, an acute toxicological study and one to observe the effect of repeat administration. The studies concluded in the third and fourth quarter 2006. In tandem, all the necessary documentation for applications to the Ethical Committee and the Swedish Medical Products Agency was compiled to enable the start of a phase I trial on healthy volunteers as soon as possible. The company was able to file the documentation with the Swedish Medical Products Agency in December.