New license agreement for rotavirus diarrhea vaccine

The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), announced today a new license agreement aimed at helping to prevent hundreds of thousands of deaths annually from rotavirus diarrhea in children living in developing countries. An effective oral rotavirus vaccine-created by NIAID scientists in the mid- to late 1980s and developed further through a Cooperative Research and Development Agreement with an industry partner-has now been licensed by the NIH Office of Technology Transfer to BIOVIRx, Inc., of Minneapolis, MN. BIOVIRx, which is responsible for obtaining requisite marketing approvals for this product, plans global commercialization of the oral vaccine (RotaShield®).

Rotaviruses are consistently shown to be the leading cause of severe diarrhea in infants and young children. Worldwide, the wheel-shaped viruses are estimated to cause more than 135 million episodes of diarrhea each year in infants and children younger than 5 years old, resulting in up to 592,000 deaths annually.

Rotaviruses are egalitarian viruses: they readily infect and cause illness in infants and young children in both developed and developing countries. The overall consequences of these illnesses, however, are quite different. Approximately 1,600 rotavirus-related deaths each day occur predominantly in the developing countries, notes Albert Z. Kapikian, M.D., who led the NIAID team that developed the vaccine and serves as head of the epidemiology section in the Institute's Laboratory of Infectious Diseases.

Symptoms of rotavirus infection develop quickly and in addition to diarrhea, may include vomiting, fever and dehydration. The resulting dehydration can be reversed through oral rehydration therapy or, in more serious cases, through hospitalization and intravenous fluids. Although effective, these therapies are not readily available or used in many parts of the developing world. Children in developing countries are more vulnerable to severe and fatal illness.

Dr. Kapikian has devoted most of his career to working on viruses that cause gastroenteritis. He and his colleagues discovered the Norwalk virus, the first virus to be established as an important cause of diarrhea. Later, he and his colleagues in NIAID developed the rotavirus vaccine that was tested in the United States and abroad in collaborative studies.

Wyeth Laboratories, Inc., manufactured the vaccine and carried out extensive field trials that led to its licensure. In 1998, the Food and Drug Administration (FDA) approved the vaccine under the trade name of RotaShield®. Subsequently, it was added to the pediatric immunization schedule and given to young infants in the United States.

More than 1 million doses were administered before the vaccine was withdrawn from the market in 1999 because of a link with an intestinal blockage known as intussusception. After continuing debate and controversy, the risk of this adverse event was estimated to be about 1 excess case per 10,000 vaccinated infants and young children. A recent scientific perspective published by NIH scientists in the Journal of Infectious Diseases, however, estimated the risk to be 1 excess case per 32,000 vaccinated infants in the target population for the vaccine, infants 45 to 210 days old. Moreover, this perspective reported an overall decrease in intussusception observed among infants less than 1 year old during the rotavirus vaccine exposure period. The background rate of intussusception in the United States is estimated to be 1 case per 3,000 infants during the first year of life.