Although the vaccine was only 48 percent efficacious against a first episode of rotavirus diarrhea of any severity, the vaccine reduced the incidence of severe rotavirus diarrhea by 88 percent and the most life-threatening symptom, dehydration, by 75 percent, and decreased hospital admissions by 70 percent.

These findings, says Dr. Kapikian, are consistent with observations of natural infection, which confers better protection against severe disease than against mild illness. "We would not anticipate that a live, attenuated vaccine would do better than wild-type virus," notes Dr. Kapikian. "The concept of eliminating the virus, like smallpox, will not occur with rotavirus," he says, "because reinfections are very common. The purpose of this vaccine is to prevent the more severe illness."

Aside from significantly greater incidence of fever in the vaccine group after the first dose only (15 percent in vaccinees versus 7 percent in controls), the two study groups experienced no differences in side effects, and the vaccine was safe and well-tolerated.

***The Vaccine***

The vaccine consists of a mixture of four viruses (hence the name tetravalent or quadrivalent) that together protect against the four most important clinical strains of rotavirus. The NIAID team designed the vaccine by substituting a gene from a human rotavirus strain for one in a weakened rotavirus that infects rhesus monkeys.

The gene contains instructions to make a protein on the virus' surface, where the immune system can easily recognize it and then tailor-make antibodies to fight that viral strain.

When making the rhesus rotavirus-tetravalent (RRV-TV) vaccine, the NIAID researchers used this substitution strategy to create weakened forms of three of the four clinically important human rotaviruses. The fourth
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Contact: Laurie K. Doepel
ldoepel@nih.gov
301-402-1663
NIH/National Institute of Allergy and Infectious Diseases
22-Oct-1997