Clinical Trials of Rotavirus Vaccines in Europe

Abstract

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 The first bovine candidate vaccine was withdrawn because of inconsistent efficacy, and studies of a rhesus rotavirus vaccine were initiated.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 However, this vaccine was withdrawn in 1999 because of association with intussusception.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.

Selección de los principales problemas de seguridad de las vacunas

“…Incluso los ensayos verdaderamente más extensos [17][18][19] , en los que se incluyeron hasta 70.000 participantes, no son capaces de detectar efectos adversos vacunales más infrecuentes que 1 por cada 10.000 vacunados. Aunque los efectos secundarios raros pueden detener en ocasiones los programas de vacunación [20,21] , los proveedores deben entender que algunas vacunas de uso corriente han mostrado efectos secundarios raros y potencialmente graves; en estos casos, las instituciones responsables de la formulación de políticas han dictaminado que los beneficios de la vacunación para los individuos y la comunidad superan a los riesgos.…”

Kernfragen der Impfstoffsicherheit

“…Unerwünschte Ereignisse im Zusammenhang mit einem Impfstoff, die bei weniger als 1 von 10 000 geimpften Personen auftreten, können selbst in den grössten Studien [17][18][19] mit bis zu 70 000 Teilnehmern nicht festgestellt werden. Obwohl es gelegentlich vorkommen kann, dass Impfprogramme durch seltene Nebenwirkungen gestoppt werden [20,21] , sollte den Impfärzten klar sein, dass auch einige der allgemein eingesetzten Impfstoffe seltene und möglicherweise ernste Nebenwirkungen haben können.…”

Immunity in the first year of life and call for vaccination

“…Rotavirus vaccine has shown around 70% seroprotection against rotavirus gastroenteritis (of any severity). For sever rota infection, the efficacy is higher and ranged from 85% to 100% as seen during various clinical trials across globe (Ruiz-Palacios et al 2006, Vesikari et al 2006). Severe rotavirus disease in humans is most common between 6 to 24 months of age.…”