Clinical trials of a live oral candidate
rotavirus vaccine were started in 1982 and soon demonstrated that severe rotavirus disease can be prevented by vaccination. The first bovine candidate
vaccine was withdrawn because of inconsistent efficacy, and studies of a
rhesus rotavirus vaccine were initiated. A field trial of rhesus-human reassortant tetravalent
rotavirus vaccine in Finland was pivotal for the licensure of this
vaccine (RotaShield) in the United States in 1998. However, this
vaccine was withdrawn in 1999 because of association with
intussusception. Safety therefore became a major issue in the development of new candidate
rotavirus vaccines. A pentavalent bovine-human reassortant
rotavirus vaccine (
RotaTeq) showed about 70% efficacy against any rotavirus disease and 100% efficacy against severe disease in Finland, according to the Clark scale. A large, multinational safety trial indicated no association of this
vaccine with
intussusception, and its licensure is under review in the EU. An attenuated human
rotavirus vaccine (RIX4414;
Rotarix) was developed from G1 rotavirus strain 89-12. A trial in Finland showed efficacy comparable with that of RotaShield, and a larger trial is under way in several European countries. In the first epidemic season,
vaccine efficacy was 73% against any and 90% against severe rotavirus (mostly G1)
gastroenteritis, according to the Vesikari scale. A large scale safety trial, conducted in Latin America plus Finland, indicated no increased risk of
intussusception among recipients of
Rotarix compared with placebo. The licensure of
Rotarix is in process in the European Union.