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The Story of Prevnar


Ronald J. Eby, Ph.D.
Dace V. Madore, Ph.D.
Velupillai Puvanesarajah, Ph.D.


Fifteen years in the making, and millions of doses of Prevnar later, the combined efforts of the three scientists and their teams have led to a great advance in child health. Since it became available in 2000, Prevnar has been called, "one of the most important advances in pediatric medicine," having systematically removed the risk of S. pneumoniae infections in children.

 


In the 1980s and 1990s, thousands of cases of pediatric pneumonia and millions of ear infections worldwide were still being caused by Streptococcus pneumoniae bacteria. The bacteria, which come in seven main forms, are also responsible for other devastating childhood infections, like meningitis (infection of the brain and spinal cord lining) and bacteremia (dangerous blood infection). Left untreated, these infections can lead to permanent organ damage and even death.

According to the World Health Organization, one million deaths worldwide in children 5 years and younger were linked to S. pneumoniae infection each year prior to approval of Prevnar in 2000. Since then it has all but wiped out invasive pneumoccal disease in young children, preventing 12,700 cases in the U.S. in 2002 alone.

The development of Prevnar is the culmination of a 15-year effort beginning with Dr. Ronald J. Eby working in his lab at Praxis Biologics (now part of Wyeth Pharmaceuticals) in Rochester, NY. Dr. Eby knew that he would need to develop new techniques to make a vaccine that would work in the undeveloped immune systems of infants. Available vaccine technology would only allow him to create a vaccine that would work in adults for this condition. The key was to change the vaccine in some way to be effective in children.

"We knew in our hearts we would succeed. The technology.. had been developed in the 1930s. Plysaccharide vaccines had also ben introduced after World War II, but they and others that followed are only effective in adults."
- Ronald J. Eby, Ph.D.


Most vaccines work by tricking the immune system into thinking that a real infection is taking place, even though it is not. Then when the person is exposed to that illness again, the immune system is already activated and ready to fend it off. Dr. Eby had to find a substance that would stimulate a strong enough immune response in the immature system of an infant to safeguard from future infection.

Existing vaccine technologies used the outer coat of bacteria to trigger an immune response from the body. Dr. Eby used this approach but linked a protein to the bacteria's outer coat that could be recognized by an infant's immune system.

The catch was that S. pneumoniae comes in seven main forms, so Dr. Eby had to create a separate compound for each of these and roll all of them into one seven-part vaccine.

Dr. Eby and his team produced numerous candidate vaccines that had the potential to be recognized by the infant immune system and provide protection against infection. Each one had to be carefully tested.

"The possibility of saving lives is why all of us enjoy working in vaccines. What is most rewarding for me is witnessing Prevnar's success worldwide in reducing diseasse incidence due to S. pneumoniae."
- Dace V. Madore, Ph.D.


Dr. Dace V. Madore, whose specialty was in clinical trials, was called upon to help in the development of a clinical program that could bring this new vaccine to the public. In order to introduce a new therapy for widespread use, scientists have to conduct rigorous studies to show that it is both safe and effective in humans.

A decade long journey took Dr. Madore from the lab to the clinic to the road. Because the vaccine was unique in that it was targeting seven forms of one bacterium, she had to develop new methods for running the clinical testing. She needed to be able to tell which parts of the vaccine were functioning well and which needed modifications. She had to run multiple trials for all the different candidates Dr. Eby's group produced and get reliable results every time. She then traveled around the country, participating in conferences and speaking at meetings, to convince the medical community to accept these new methodologies for vaccine testing.

Once the vaccine was shown to be safe and effective, the challenge of making the quantities of vaccine required for the millions of children worldwide was left to Dr. Velupillai Puvanesarajah. He had already made the 30,000 to 40,000 doses that clinical trials alone required and now 10,000 times that number would be needed for distribution on the millions of children.

"When people tell me how many lives have been saved, I must admit that I feel really good. It's very rewarding to actuallly have an impact on peoples health."
- Velupillai Puvanesarajah, Ph.D.


Developing a way to produce enough vaccine without compromising quality or safety was quite an undertaking. The large-scale production of this vaccine required an innovative multi-step process to ensure safety and consistency from batch to batch. The resulting manufacturing process, equipment and facilities pioneered by Dr. Puvanesarajah have successfully manufactured more than 72 million doses of Prevnar to date.

The impact of the vaccine on child health has been dramatic. The development of this type of vaccine has "represented the greatest vaccine breakthrough of the late 20th century," according to Jeffrey Baker and Samuel Katz of Duke University Medical Center.

These scientists have demonstrated the creativity, resolve, and cooperation needed to bring a successful therapy to the public. Their impact on the world at large is illustrated by the hundreds of thousands of lives saved.

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