Fig. 1. (A) Schematic figure of the DNA construct encoding the ORO vaccine antigen. The signal sequence (derived from human BM40) is marked by an S. An asterisk denotes an unpaired cysteine residue that was changed to serine by point mutagenesis. (B) Structure of the recombinant ORO protein.
It should be possible to use therapeutic vaccines to create both cheap and effective drugs for diseases like cancer and allergies. One problem in developing such vaccines has previously been the lack of adjuvants, substances that make vaccines more effective. However, there has now been a major breakthrough in this area. “We have made a very important breakthrough by managing to identify a substance that is biologically degradable and that exhibits considerably higher activity than the adjuvants that have been used in the past,” says Lars Hellman. “These new and highly promising findings are an important step toward developing more cost-effective drugs for some of our major public health diseases,” he says.
Many of the treatment methods that are developed today for allergies, cancer, and autoimmune diseases are based on the use of so-called monoclonal antibodies. The cost of these protein pharmaceuticals is high, between 15,000 and 150,000 dollars per patient and year, and long periods of treatment are often needed. Therapeutic vaccines contain no pre-produced antibodies but rather stimulate our immune system to produce its own therapeutic antibodies. They are considerably less expensive to manufacture than the drugs that are now being produced.
“Therapeutic vaccines that target the same molecules in the body as the various monoclonal antibodies would enable us to reduce the cost of treatment significantly, and also decrease the number of visits patients need to make to the clinic,” says Lars Hellman, professor of molecular and comparative immunology at the Department of Cell and Molecular Biology, Uppsala University, who directed the study.
Monoclonal antibodies are used successfully in the treatment of many human disorders. However, these antibodies are expensive and have in many countries put a major strain on the health care economy. Therapeutic vaccines, directed against the same target molecules, may offer a solution to this problem. Vaccines usually involve lower amount of recombinant protein, approximately 10,000–20,000 times less, which is significantly more cost effective. Attempts to develop such therapeutic vaccines have also been made. However, their efficacy has been limited by the lack of potent immunostimulatory compounds, adjuvants, for human use. To address this problem we have conducted a broad screening for adjuvants that can enhance the efficacy of therapeutic vaccines, whilst at the same time being non-toxic and biodegradable. We have now identified adjuvants that show these desired characteristics. A combination of Montanide ISA720 and phosphorothioate stabilized CpG stimulatory DNA, induced similar or even higher anti-self-antibody titers compared to Freund’s adjuvant, currently the most potent, but also toxic, adjuvant available. This finding removes one of the major limiting factors in the field and facilitates the development of a broad range of novel therapeutic vaccines.