Novel vaccines in works for three disease states

Novel vaccines in three areas of research were the subject of the Ambulatory Care PRN Focus, held at the American College of Clinical Pharmacy's annual meeting in Denver in October. Mary S. Hayney, Pharm.D., MPH, presented vaccine candidates for the prevention or treatment of malaria, HIV, and nicotine addiction.

"There is a complex genome and complex life cycle of this parasite" associated with malaria, Hayney told the audience. Hayney, an associate professor of pharmacy at the University of Wisconsin School of Pharmacy, explained that one obstacle is the various antigenic presentations of malaria in humans that make a vaccine difficult to develop. She added that affordability is another obstacle. "The areas of the world with the highest burden of malaria are also the poorest, with the fewest resources," she said. In addition, the ability to transport and administer this vaccine to remote areas will likely be other important issues that will need to be addressed.

Despite the obstacles, there are several strategies for developing a malaria vaccine. "We do know that induction of CD8+ T cells is particularly important in the liver stage of the disease," said Hayney. Another approach is the prime-boost strategy where you "prime" with one recombinant vector and boost with a different one. "You use the same antigen, but you show it to the immune system in a different way such that your body magnifies the response to the antigen," she explained.

HIV vaccines were the subject of the second part of Hayney's presentation. "Obstacles to HIV vaccine development include the genetic diversity of the virus and how easily it mutates. You can have many different types within one individual," she pointed out. "There have been millions of documented cases of HIV and yet no documented case of long-term immunity."

One promising candidate in the pipeline is a joint effort between Sanofi-Pasteur and VaxGen. Currently in a Phase III trial in Thailand, the vaccine is a canarypox vector vaccine with rgp120 subunit boost. The strategy is to induce both cellular and humoral immunity. Preliminary study results are expected in 2009.

A second product that is not quite as far along comes from the Vaccine Research Center at the National Institutes of Health's National Institute of Allergy and Infectious Diseases (NIAID). Phase II studies are currently underway for this vaccine that utilizes plasmid DNA inserted into a recombinant adenovirus. "It is hoped it will induce strong cellular immunity," said Hayney. Phase III studies are slated to begin in early 2008.

With 1.3 billion tobacco users in the world and nicotine as the major mediator for tobacco addiction, a successful anti-nicotine vaccine could be a true life-saver. One vaccine in development uses antibodies that bind to nicotine and prevent it from crossing the blood-brain-barrier. Because nicotine itself is not terribly immunogenic, it must be conjugated with something else, according to Hayney. "Scientists have conjugated nicotine to a protein which is recognized by the immune system and really does elicit an immune response," she said. That protein is recombinant Pseudomonas aeruginosa exprotein A.

The product, NicVax from Nabi Biopharmaceuticals, is currently in Phase IIb trials and preliminary evidence suggests the height of antibody response correlates very strongly with smoking abstinence. "So, the higher you can boost your nicotine antibody with the vaccine, the more likely you are to not smoke," Hayney explained. But one potential question that has not yet been answered is whether or not the antibodies will become saturated – a situation where you could simply smoke more and saturate and overcome the antibody system.

"It will require multiple doses – this will not be a one shot kind of thing," said Hayney of NicVax. "This is likely to be a vaccine that requires frequent boosters to maintain antibody response." The FDA has granted this vaccine fast-track status.