A team of Yale researchers announced Thursday that it has developed an inexpensive and easily administered AIDS vaccine that prevents the disease in monkeys and may work in humans.
The vaccine, developed over the last six years by Dr. John K. Rose and his team at the Yale School of Medicine, will be administered as a nasal spray. It can be produced at a low cost and may allow protection against several strains of HIV. If proven effective in humans, the vaccine could help slow an AIDS epidemic that began more than 20 years ago and has since claimed the lives of 22 million people worldwide.
The drug must be subjected to several clinical trials before it can be marketed. That process is at least three years long.
Although there are several other AIDS vaccines undergoing testing, all of them require multiple injections and, in many parts of the world, it may be impossible for doctors and relief workers to get people to return for the many injections.
“In the developing world and areas that have been hit hard with HIV and AIDS, it would be impractical and very expensive to inject millions of people with DNA vaccines,” Rose said from Philadelphia Thursday where he presented his findings at the AIDS Vaccine 2001 Conference. “This is a cost-effective and equally successful alternative to other vaccines being tested that require the use of needles. This will be an extremely easy method to use on children and will require probably only one or two treatments.”
Dr. Carl Dieffenbach, acting chief of the National Institute of Allergy and Infectious Diseases vaccine research branch, said he expects the new AIDS vaccine will be comparable to the polio vaccine, which needs to be administered only once or twice to take effect.
The Yale AIDS vaccine project has been entirely funded through the initial testing phase by the National Institutes of Health. Now that the vaccine has proven effective in animals, Wyeth-Lederle, a vaccine company that is a division of corporate giant American Home Products, will help to accelerate it through the human testing phases.
The key to the team’s success is their novel vaccine delivery system, called a vector. The vector, a weakened virus, encodes AIDS virus proteins and introduces them into an animal in order to create an immune response.
For the last six years Rose and his team have been working on the vesicular stomatitis virus (VSV) as their vector.
After noticing that weakened VSV vectors encoding either influenza virus proteins or proteins of the measles virus produced immunity in mice, Dr. Rose decided to use VSV as a delivery system for AIDS.
The research team vaccinated seven monkeys using a VSV vector encoding AIDS virus proteins. Next, they infected the seven vaccinated monkeys and a control group of eight unvaccinated monkeys with a virus that is a hybrid between human AIDS and a monkey AIDS virus.
“We found that animals that did not receive the vaccine typically developed AIDS in three to six months,” Rose said. “But vaccinated monkeys have been AIDS-free now for 14 months.”
An important problem that Rose’s vaccine overcomes is that of the many existing strains of HIV. Some other vaccines are designed to produce antibodies that recognize the surface protein of HIV. But the ability of the HIV surface protein to change its configuration often causes the virus to go unnoticed by most antibodies.
Rose’s approach overlooks the surface protein. Instead, his vaccine stimulates immune cells that recognize small protein fragments that are highly conserved sequences in a variety of HIV strains.
“The weakened virus that we engineered and used to vaccinate monkeys does not cause any disease but produces strong immune responses to the AIDS virus proteins,” Rose said. “When later challenged with an AIDS virus they become infected initially but then control or clear out the infecting virus.”
The vaccine still has several years of expensive development and testing to undergo. First, working with Wyeth-Lederle, the team must make it into a product that meets Food and Drug Administration rules and regulations, an approval process that can take roughly one year. When this is accomplished, NIH will put the vaccine through three phases of limited human clinical trials that could take at least two to three years.
But NIH officials who have overseen the development of the pre-clinical vaccine are confident it will advance swiftly.
“The beauty of Dr. Rose’s work is that he created a strong partnership between himself and two other important branches,” Dieffenbach said. “In addition to federal support from NIH, he is linked to Wyeth-Lederle, a drug company that has the deep pockets to push this new product through the clinical phases of testing.”
Dieffenbach added that one possible pitfall the vaccine could face is that, as of now, it has only been tested and proven effective in monkeys.
“The vaccine is currently imperfect because it is only a model but that should not be a huge problem,” Dieffenbach said. “The AIDS virus used in the pre-clinical trials was a hybrid between the human and monkey virus, which shows promise. Also, working with a major vaccine company that put the flu vaccine on the market should ensure that this moves along as quickly as possible.”