Josephine van Dongen

Chapter 1 12 Product and manufacturer Type of vac- cine Indication License Availability Efficacy* P2-VP8-P[8] subunit (Wal- ter Reed Army Institute of Research Pilot Bio-production Facility) Non-replica- ting, monova- lent, parental To be deter- mined No Phase 3 (>98% sero- conversion) 38 P2-VP8-P[4] P[6]P[8] su- bunit (Walter Reed Army Institute of Research Pilot Bio-production Facility) Non-replica- ting, trivalent, parental To be deter- mined No Phase 3 Not available *Efficacy against severe rotavirus acute gastroenteritis after vaccination in the first year of life.Abbreviations: CI = confidence interval,WHO =World Health Organization. Current rotavirus vaccines Four different rotavirus vaccines are currently licensed worldwide. 38 Two of these live-attenu- ated vaccines have been licensed in Europe and three additional vaccines are currently being evaluated. 38,40 More inactivated vaccine candidates are under development. 38 The characteristics of different rotavirus vaccines are presented in table 1 . The vaccines have been studied and developed exclusively for infants. Live-attenuated vaccines function by mimicking natural rotavirus infection.The live-attenuated virus type(s) contained in the vaccine infects the intestinal epithelium and induces an immune response, which is similar to a natural rotavirus infection. A complete vaccine course (multiple doses) provides a broad protection against diverse genotypes (i.e. both homotypic and heterotypic immunity). 41,42 The two live-attenuated rotavirus vaccines that are globally available, RotaTeq and Rotarix, were investigated for efficacy and safety in large international phase III clinical trials with in total over 150.000 infants included. Highest efficacy for rotavirus vaccination was measured in Europe and Nor th-America, 80 to 100%, against severe rotavirus gastroenteritis caused by diverse rotavirus genotypes. 36,37,43–45 Efficacy in developing countries yielded clearly lower estimates, 40 to 70%. 46,47 Proposed mechanisms for a lower efficacy are higher maternal antibodies, intestinal dysbiosis and a different host response. 48,49 There was a need for better rotavirus vaccines for developing countries.To address the problems of vaccine performance in these countries, other (parental) vaccines were developed.Vaccine efficacy for these newer vaccines in phase III trials seems indeed better, depicted in table 1 . Vaccine performance in medical risk infants (i.e. those born premature, with low bir thweight