Physicians at the University of Rochester Medical Center are beginning the world's first test in humans of a potential vaccine to protect against human papillomavirus (HPV) infections, one of the most common sexually transmitted diseases. Physicians estimate that 20 to 40 million people in the U.S. alone carry HPV, which causes warts of the genital tract and causes nearly all cases of cervical cancer in women.
The vaccine, developed by University researchers working together with scientists at MedImmune, Inc. of Gaithersburg, Md., will be tested at the University during the next year in healthy volunteers who have no symptoms of HPV infection. The study will be led by Richard Reichman, M.D., director of the Infectious Diseases Unit of the Department of Medicine and professor of medicine and microbiology and immunology. The Food and Drug Administration cleared the study in December.
Several scientists and physicians have contributed to the development of the vaccine. In addition to Reichman, Rochester members of the team include Robert C. Rose, Ph.D., senior instructor in medicine, and William Bonnez, M.D., associate professor of medicine. The three are members of the Infectious Diseases Unit of the Department of Medicine. Also collaborating with MedImmune on the technology are scientists from Georgetown University, the German Cancer Institute, and the National Institutes of Health.
"HPV infection is very, very common, affecting up to 40 percent of people in certain age groups, such as sexually active men and women under the age of 30," says Reichman. "This vaccine approach has proven safe and effective at preventing similar infections in animals, and we're hopeful that comparable results will be obtained in humans as well."
The year-long study is to verify the safety of the compound and to check whether it causes the desired immune response -- the formation of antibodies to HPV.
The key to the vaccine is a genetic technology designed to trigger an immune response. The Rochester team cloned the gene that codes for the virus's protein envelope or "capsid," then used a cell line derived from insects to make a large amount of virus-like particles. The particles are not infectious, and they share few traits with real HPV except for their shape. That could be enough for a vaccine, though, since it's the shape of a particle that often marks it as an invader and spurs the body to mount an immune attack.
One of the reasons HPV has eluded vaccine makers is that the virus, unlike herpes or the flu or even HIV, won't grow in a laboratory dish, making it extremely difficult to study. The Rochester team was one of few to find a way to use mice to grow large amounts of the virus for study.
HPV actually stands for a family of more than 75 closely related viruses. A few are harmless and cause such nuisances as warts on the hands or plantar's warts on the feet, but as many as 30 infect the genital tract, causing warts that are difficult to treat and that recur often. Of those 30, a handful cause nearly all of the 15,000 cases of cervical cancer that occur in women in the U.S. alone every year. About 5,000 women in the U.S. die of the disease every year; in some areas of the world, HPV-induced cervical cancer is the leading cause of death by cancer in women.
Since there are so many different HPV types, any vaccine will have to protect against several of them, much like polio and pneumonia vaccines do. While the trial vaccine is targeted against only HPV type 11, researchers have already produced virus-like particles against several other types. Those could be incorporated as part of a broader vaccine.
If the current study shows that the vaccine is safe and able to provoke an immune response, the next step will probably be an even larger study, says Reichman. It usually takes at least four years to completely evaluate a vaccine.
The University has filed for a patent on the HPV vaccine technology and has licensed the rights to MedImmune, a biotechnology company that develops and markets products for the prevention and treatment of infectious diseases and for use in transplantation medicine.