Vaccine With University of Rochester Roots Saves Thousands from Illness

April 30, 2003

A vaccine that had its start in basic research two decades ago at what is now Golisano Children’s Hospital at Strong has shown remarkable success, causing rates of infection by a persistent microbe to plummet by 69 percent nationwide in the span of just three years.

The success of the Prevnar vaccine, produced by Wyeth after the company licensed basic technology from the University of Rochester Medical Center, is covered in the May 1 issue of the New England Journal of Medicine. The numbers translate to roughly 20,000 fewer cases of infection each year in the United States, with the greatest prevention among the youngest children.

Prevnar was introduced in 2000 to prevent invasive infections by pneumococcal bacteria, which cause meningitis, ear infections, pneumonia, and other maladies – researchers say that in the developing world, about 1 million people die each year of infections caused by the bacteria. The new study shows that the rate of infection among children less than two years of age in seven cities around the nation, including Rochester, fell 69 percent from 1998 to 2001. Surprisingly, the rate of infection in unimmunized adults dropped as well, probably because the vaccine eliminated or reduced the number of germs in children who normally serve as reservoirs of Pneumococcus.

In Rochester, the effects were even more noteworthy: The vaccine slashed infection in children under age 2 by 83 percent. Nancy Bennett, M.D., clinical associate professor and deputy director of the Monroe County Health Department, helped analyze the rates of infection in the Rochester area, along with project coordinator Christine Long.

"The vaccine’s real-world performance is remarkable," says Richard Insel, M.D., the University of Rochester scientist who had a hand in creating the technology more than two decades ago.

"Of course the vaccine looked very good in the laboratory and in efficacy field trials, but this is very, very good news under real-world conditions," says Insel, who notes the effectiveness of the vaccine despite periodic shortages. "The data on decline in rates of invasive disease in adults, who were not immunized, is fascinating as well. The vaccine seems to impose a type of ‘herd immunity,’ where the adults around these children are protected as well. This is quite heartening."

Physicians at the university are currently conducting a study to see if Prevnar is also effective in preventing pneumonia in elderly patients.

It was a team comprised of Insel, David Smith, M.D., and Porter Anderson, Ph.D., that was one of the first to develop and test the concept of a "conjugate" vaccine, a method to make a vaccine more effective by linking it to a protein that would spur an infant’s immune system to fight an infection especially vigorously.

Insel, who is currently director of the university’s Center for Human Genetics and Molecular Pediatric Disease, and his colleagues showed that the coupling of a protein to an existing polysaccharide vaccine evoked an immune response in infants that could not be elicited with the plain polysaccharide vaccine alone. The new Prevnar vaccine includes a mutant form of diphtheria toxin that spurs the immune system to fight the Pneumococcus microbe effectively.

Pneumococcus is the second microbe to be targeted by a "conjugate" vaccine based on the Rochester technology. A decade earlier the team first used the technology to take aim at a bacteria known as Haemophilus influenza type b (Hib). After successful initial tests in the early 1980s, the team tried to persuade a pharmaceutical firm to license the technology.

Vaccine research wasn’t especially popular in the industry at the time, and the offer was declined. So the group headed by Smith went into business together and created a company, Praxis, to make the vaccine. The HIB vaccine was approved by the Food and Drug Administration in 1990 – at that time the first vaccine in 20 years to be recommended by FDA for universal use in children – and has virtually wiped out infection by the microbe, which was a leading cause of meningitis in preschoolers. Illnesses caused by this disease in the United States have fallen from 20,000 each year to about 200 cases since the introduction of the HIB vaccine.

"The Haemophilus influenzae pathogen was the most common cause of meningitis in children, as well as the most common cause of acquired mental retardation and acquired deafness in children," says Insel. "During my training in the 1970s, you could walk into any pediatric ward anytime and guarantee that there would be at least one child with invasive Haemophilus influenzae. Now, there are so few cases, a doctor will go years without ever seeing a case."

A third conjugate vaccine based on the technology, targeted against the microbe meningococcus, is available in some parts of the world, including the United Kingdom. This is the bacteria that causes spinal meningitis and bloodstream infections that are extremely contagious and sometimes kill previously healthy people very quickly.

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