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Efforts of NIAID Scientists Led to First Licensed Rotavirus Vaccine

Human rotavirus particles from a stool sample.
Credit: NIAID

Rotavirus is the most common cause of severe childhood diarrhea worldwide, responsible for more than 500,000 deaths each year in children less than 5 years old, according to Centers for Disease Control and Prevention (CDC) estimates. In 1974, NIAID scientists led by Albert Kapikian, M.D., were the first to identify human rotavirus in the United States (rotavirus was first discovered in Australia in 1973) and began what would be a decades-long effort to develop a vaccine. The researchers defined the mode of transmission of the virus, identified the viral proteins critical for triggering an immune response, and developed methods for reassorting the virus that are still in use today.

Their efforts, in partnership with Wyeth-Ayerst Laboratories, led to the development, testing, and approval in 1998 of RotaShield, the first Food and Drug Administration-licensed rotavirus vaccine. Clinical studies showed that the oral vaccine was safe and highly effective in preventing severe rotavirus diarrheal disease, with a protective efficacy of up to 91 percent.

The success of RotaShield was temporary, however, as post-marketing studies linked the vaccine to a higher risk of bowel obstruction (intussusception) among the vaccine recipients. CDC estimated that 1 or 2 extra cases of intussusception would be caused among each 10,000 infants who received the vaccine. At the time, the background rate of intussusception in the United States was estimated to be up to 1 case per 2,000 infants less than 1 year old. As a result, CDC’s Advisory Committee on Immunization Practices withdrew its recommendation to vaccinate infants with RotaShield, and the manufacturer voluntarily withdrew the vaccine from the U.S. market in 1999.

Further analysis conducted after RotaShield’s withdrawal suggested that “catch-up” vaccination of older infants (first dose given after the recommended age of 2 months) contributed disproportionately to the increased number of intussusception cases among vaccine recipients. Moreover, no cases of intussusception were recorded within 21 days after receiving the first dose of RotaShield in approximately 70,000 infants less than 60 days old. The age factor would prove important in the development of strategies for rotavirus vaccines under development.

Though the vaccine’s risks were considered unacceptable in the United States, scientists argued that RotaShield’s protective benefits could save thousands of lives in developing countries, where most rotavirus-associated deaths occur. The vaccine has since been licensed to a U.S. nonprofit organization and is undergoing a trial in nearly 1,000 infants in Ghana to evaluate the efficacy of two oral doses: one administered soon after birth and another before the infant is 60 days old, a period when the development of intussusception under natural conditions is less common.

A second-generation rotavirus vaccine developed by Dr. Kapikian and colleagues has been licensed by pharmaceutical companies in Brazil, China, and India. These companies can produce the vaccine locally at much less expense than importing it from elsewhere, raising hopes that children in developing nations will one day have greater access to an affordable rotavirus vaccine.

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Last Updated September 10, 2010