Taking Rotavirus Vaccine From the Lab to the World
In February 2006, the European Union (EU) announced that the rotavirus vaccine Rotarix™, developed and first tested by Cincinnati Children's researchers Richard Ward, PhD, and David Bernstein, MD, was approved for commercial use in its member countries. The addition of the EU countries brings the total to more than 60 countries now providing this vaccine to their children.
Dr. Dick Ward at workin his lab at Cincinnati Children's. He has spent close to 20 years developing the rotavirus vaccine Rotarix, now availablein more than 60 countries.
For Dr. Ward, a professor in the Division of Infectious Diseases at Cincinnati Children's, the EU's announcement marked the culmination of nearly two decades of effort to advance the vaccine from its inception in the lab to its approval and widespread use throughout the world.
Why Focus on Rotavirus?
It was not until 1973 that human rotavirus was identified as the cause of severe childhood diarrhea. In the United States and most European countries, serious rotavirus cases occur, but the final outcomes are often very different from those that occur in developing countries where fewer medical resources and poor nutritional status lead to high death rates in children.
According to Dr. Ward, approximately 600,000 children throughout the world die each year from rotavirus infections. Pediatricians consider it the sixth most serious infectious disease that can affect children younger than 3 years old.
Developing the Vaccine
Developing a vaccine, licensing it and getting it approved by countries throughout the world are not easy ventures. During the early development stages of any vaccine, the odds of completing all the needed clinical trials and successfully marketing the final product are understandably slim.
Researchers originally looked into producing a rotavirus vaccine using animal strains of the virus. In fact, the first vaccine to make it to market, RotaShield™, appeared in the USA in 1998 and was derived from a bovine strain of the virus. RotaShield was subsequently pulled the following year due to an association with an unacceptably large number of cases of intussusception.
Dr. Ward began his own research into a rotavirus vaccine after joining the Gamble Institute, which became part of Cincinnati Children's in 1995. He theorized early on in his research that a weakened single human strain of the rotavirus might be more effective than the animal strains that had been used to that point. There are multiple serotypes of rotavirus but "we felt there was evidence from 'Day 1' that it may not matter what serotype was used," says Dr. Ward. "We concluded that a single human strain might give the same level of protection as multiple animal strains." Using the model developed by Albert Sabin, MD, at Cincinnati Children's to produce the oral polio vaccine, Drs. Ward and Bernstein developed the model still used today to produce the only vaccine derived entirely from a virulent human rotavirus weakened during multiple passages in cell culture.
Extensive Testing
Following the development of the vaccine, extensive clinical trials took place under the sponsorship of Avant Immunotherapeutics, Inc., which licensed the product in 1994. The definitive efficacy trial for infants began in 1996 and resulted in a publication in the journal Lancet in 1999 showing that the vaccine was 89 percent efficacious against all rotavirus disease. Shortly thereafter, pharmaceutical giant GlaxoSmithKline (GSK) came on board and sublicensed the vaccine. Once a large pharmaceutical company was in place to produce the vaccine, multiple large-scale clinical trials were launched, mainly in Latin America. These trials proved that the vaccine, now marketed by GSK as Rotarix, was safe and highly efficacious against multiple strains of rotavirus, including those with different serotypes than the vaccine itself.
Giving Hope to Kids Worldwide
Dr. Ward is pleased that the vaccine has made it this far against such overwhelming odds. "Were there times when we didn't think it would go forward – when we saw 5,000 hurdles in front of us and all of them getting bigger? Yes, there were," he says. "The first hurdle was isolating a rotavirus strain that could be used to develop the vaccine itself. But once we did that, we still needed to get good responses. We had no idea whether the vaccine strain would be sufficiently attenuated and, if so, would still provide effective protection."
Now, with more than 60 countries having access to Rotarix – and with the anticipated addition of the US in 2007 – there is hope that rotavirus will be prevented, and children who would otherwise die from infection will survive.
Dr. Ward is research professor of pediatrics in the Division of Infectious Diseases. His recent studies have been published in Current Opinion in Investigational Drugs 2005;6(8):798-803 and the Journal of Infectious Diseases 2005;192 (Suppl 1):S30-S35.
