RotaShield®: An Oral Rotavirus Vaccine

More than half a million children – or 1,400 to 1,600 each day – die from rotavirus, the most common cause of severe childhood diarrhea. Almost all of these deaths occur in developing countries, where lifesaving medical care may not be affordable or available to the families with the most critical needs.

To combat rotavirus, the International Medica Foundation is currently conducting a Phase II clinical trial of its oral rotavirus vaccine, RotaShield®, in more than 1,000 newborn infants in Ghana, Africa, in association with the Noguchi Memorial Institute for Medical Research.

The two current rotavirus vaccines on the market are used in the United States and internationally by those who can afford them, or in a few countries through subsidies or government support, but economic issues prevent the majority of the families in need in developing countries from access to a cost-effective rotavirus vaccine. In addition to RotaShield costing less, the International Medica Foundation's strategy for sustainability of this vaccine in developing countries includes ultimately providing the manufacturing know-how and assistance to developing countries with the infrastructure to produce vaccines.

RotaShield originally was created by National Institutes of Health scientists led by Albert Z. Kapikian, M.D., and was further developed by Wyeth. The U.S. Food and Drug Administration (FDA) licensed RotaShield in 1998 to be administered in three oral doses at two, four and six months of age. When the vaccine was administered to older infants outside of the approved FDA dosage schedule there was an association with an intestinal blockage called intussusception in some older infants. As a result, the manufacturer voluntarily withdrew RotaShield from the market in 1999. The FDA's more recent approval of the two latest rotavirus vaccines have required well-defined age limits in the infants being administered those oral rotavirus vaccines.

Recent scientific evidence supports the safety of RotaShield when it is administered to infants at the appropriate age and it is not associated with intussusception. In one specific example (J Infect Dis. 2005:195(Suppl)S36-S43) a data set of 433,222 infants were administered RotaShield, and there were no cases of intussusception in all of the infants who were administered the first dose of RotaShield when they were less than 60 days of age at the time of receiving the first dose.

This new clinical trial in Ghana uses only two oral doses of the vaccine intended to be given very early in life, with the first dose being administered soon after birth and the second dose before the infant is 60 days old. Four separate clinical trials had been conducted in the past with RotaShield in which infants safely received the first dose of RotaShield within weeks of birth. In a very recent publication (Pediatrics. 2009;123:744-749) retrospective analysis has shown that when infants only received two doses of RotaShield in the United States, the vaccine appeared to be effective in preventing hospitalizations and emergency visits for all-cause acute gastroenteritis.

Neonatal dosing of RotaShield presents the promise of a number of advantages. First, it offers protection from disease at an earlier age; rotavirus in developing countries strikes infants at a younger age than in industrialized countries. Up to 15 percent of rotavirus illness occurs before three months of age in developing countries. Second, neonatal dosing would fit with the World Health Organization (WHO) schedule that includes a BCG vaccine at birth and the three remaining immunization visits at six, 10, and 14 weeks, therefore, neonatal dosing is an ideal time to give a vaccine in developing countries since that is when most infants will come in contact with a health care provider. Third, the neonatal schedule of two doses versus the original three-dose schedule would significantly reduce the cost of providing vaccine to a large number of infants. Finally, neonatal dosing minimizes the risk of intussusception associated with dosing at an older age.

Upon competition of the current Phase II clinical trial of RotaShield in newborns, the International Medica Foundation plans to conduct additional trials in other developing countries prior to applying for regulatory approval to provide the vaccine to families in need throughout the African continent and globally.