For Provenge the patients' blood cells are incubated with a fusion protein (PA2024) consisting of two parts, the antigen prostatic acid phosphatase which is present in 95 percent of prostate cancer cells, and an immune signaling factor GM-CSF as an adjuvant. The fact that Provenge is the only approved therapeutic cancer vaccine out of hundreds that have been tested in clinical trials shows just how hard the cancer vaccine field is. However, a large amount of knowledge has been accrued over the years about the mode of action of cancer vaccines and hence it might be predicted that more effective cancer vaccines will evolve over time and hence this remains an exciting and promising area of unconventional vaccine development.

Another promising area of unconventional vaccine development is allergy. In the US, approximately 20 percent of the population or 65 million people have an allergy. Allergy to grasses represent close to 50 percent of all allergies, with allergies to animals representing around 30 percent and food allergies comprising of 10 percent. Allergy desensitization therapy involves administration of progressively higher doses of allergen with the subject requiring lifelong boosters.

Recent attempts have been made to simplify desensitization to just a short course of two-to-three vaccinations using an adjuvant to induce long-term immunity. Our company, Vaxine, is developing a promising allergy vaccine against life threatening anaphylaxis from insect sting allergies, incorporating the proprietary delta inulin adjuvant, Advax, with promising results in an ongoing human clinical trial of bee venom allergy.

Allergy Therapeutics has developed a vaccine called Pollinex Quattro, based on MPLA, for the treatment of ragweed allergy. Cytos Biotechnology has developed CYT003-QbG10, an allergen-independent immunodrug, which in phase I clinical trials in allergic asthma and rhino-conjunctivitis was well tolerated and is now in phase II clinical development for allergic asthma. CYT003 comprises the virus-like particle Qb, filled with a synthetically produced bacterial DNA that activates the immune system via TLR9. Overall, the application of new delivery and adjuvant technologies to allergy vaccines represents a relatively low-risk, high-return, approach within the unconventional vaccine area.

Considerable effort has also gone into developing vaccines that protect against Alzheimer's disease. The first vaccine against Alzheimer's disease was Elan Pharmaceuticals' AN-1792 vaccine, which successfully reversed amyloid-β deposits and memory loss in transgenic mice. But in humans, AN-1792 was somewhat of a disaster with Elan having to halt a large clinical trial after some patients developed meningo-encephalitis. A phase II trial of bapineuzumab, Elan's passive anti-amyloid-β antibody infusion showed little clinical benefit and at high doses caused brain swelling and associated microbleeds in some patients.