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Nasal Vaccine Prevents SARS Infection in Monkeys

Focusing on respiratory tract may raise vaccine's effectiveness in humans

THURSDAY, June 24, 2004 (HealthDayNews) -- Monkeys given a new intranasal SARS vaccine showed no sign of developing the illness after being exposed to the virus, researchers report.

The success of the vaccine in monkeys is "a good sign with regard to likely success in humans," said study senior investigator Peter L. Collins of the National Institute of Allergy and Infectious Diseases.

"One advantage of this vaccine is that it is designed to be administered intranasally and provides direct immunization of the respiratory tract, which is the major site of SARS transmission, replication and disease," Collins said. The two other SARS vaccines described to date are both administered via intramuscular injection.

The new study is published in the June 26 issue of The Lancet. A second, related study, conducted by the same team of National Institutes of Health researchers, was published earlier this week in the online edition of the Proceedings of the National Academy of Sciences.

SARS first surfaced in southern China in late 2002. During the next six months, the disease infected more than 8,000 people worldwide, resulting in nearly 800 deaths in 27 countries. Caused by a previously undiscovered coronavirus, the respiratory illness usually begins with a fever of more than 100.4 degrees Fahrenheit. Other symptoms can include chills, headache, body aches and general discomfort.

After the worldwide concern caused by the 2002-03 SARS outbreak, the race began to find an effective vaccine against the illness. In April of this year, scientists announced the development of a DNA-based vaccine that seemed to prevent the illness in mice. However, many experts remain skeptical that DNA vaccines can be used effectively in humans.

In their study, Collins and his team developed a new intranasal vaccine that "piggybacks" a piece of a SARS virus protein onto a weakened form of the parainfluenza virus -- a germ that can cause serious flu in children.

The protein, called SARS S, "is a viral surface protein that was suspected to be important in inducing protective immunity against the SARS virus," Collins explained.

Vaccines typically use a weakened form of virus, or a virus fragment, to "prime" the body against real infection later on. In this case, Collins designed the parainfluenza/SARS vaccine as a nasal inhalant, to better protect the respiratory tract.

His team exposed eight African green monkeys to the SARS virus. Four of the monkeys had received an intranasal dose of the vaccine a month prior to exposure with the virus, while the other four had not.

Testing the vaccinated animals over a period of two weeks following exposure to the virus, "we could not detect any shedding of [SARS virus] in nasal and respiratory tract secretions," Collins said. On the other hand, each of the four unvaccinated primates displayed signs of being actively infected.

These findings were confirmed in a separate study published in this week's Proceedings of the National Academy of Sciences. In that study, Collins' team administered the same vaccine to hamsters, then examined the rodents' lung tissues for traces of the SARS virus.

"None was found, confirming the effectiveness of the vaccine," Collins said.

In a prepared statement, Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, said the findings "demonstrate the outstanding progress we have made against this newly recognized and deadly disease."

Dr. Robert Garry is a microbiologist researcher at Tulane University. He said that while all of the SARS vaccines currently under development have "seemed to be pretty effective," the next hurdle will be to see if they work as effectively in humans as they have in animal models.

"Usually it's a pretty good bet that if you can protect animals against the virus, you can probably do that for humans," Garry said. "But that remains to be determined."

Collins stressed that roadblocks remain. Because most adults have already built up immunity to parainfluenza virus, any vaccine relying on that pathogen would most likely only be effective in infants and small children. He said his team plans to focus next on another strain of parainfluenza virus "that does not commonly infect humans, and so should be able to efficiently immunize adults."

And he stressed that these types of vaccines would be used solely for prevention, not as a treatment in individuals already infected with SARS. According to Collins, experts still don't understand SARS well enough "to know if vaccination during infection would halt disease progression. My guess is that it would not be effective."

Still, he remains optimistic that an effective vaccine will be found.

"Some viruses are very challenging when it comes to vaccine development: the most obvious example is HIV," he said. "Compared to this, the experience so far with SARS suggests that development of an effective vaccine will be a much easier task."

More information

Visit the National Institute of Allergy and Infectious Diseases for more on SARS.

SOURCES: Peter L. Collins, Ph.D., senior investigator, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Md.; Robert Garry, Ph.D., professor, microbiology, Tulane University, New Orleans; June 26, 2004, The Lancet; June 21-25, 2004, online edition, Proceedings of the National Academy of Sciences
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