Josephine van Dongen

Chapter 8 192 Infant population characteristics Another possible explanation for the lower vaccine effectiveness is related to the study population. Some host-factors are known to influence the rotavirus vaccine immune response, including gut dysbiosis, genetic factors and intestinal coinfections.While these associations have mainly been established based on studies in developing countries, 44 they may also be relevant for infants with MRC. For instance, gut dysbiosis may also exist in medical risk infants because of prematurity, antibiotic treatment or critical illness. Microbiome composition is additionally thought to differ from term infants, depending on gestational age. These differences, also in microbiota with positive effects on immune training, were described to exist at six weeks of age (the time point of first rotavirus vaccination). 45 In addition, premature infants have impaired functioning of the mucosal barrier, and innate and adaptive immune system. 46 This may contribute to decreased effectiveness of mucosal vaccines in premature infants as was demonstrated for oral polio vaccines. 47,48 Fur thermore, infants with congenital cardiovascular pathologies, that comprised the largest group of congenital disorders in our study population, are known to be immunocompromised pre- and post- cardiac bypass surgery, or may suffer from genetic disorders affecting the immune system and consequently rotavirus vaccine immune response. Serum anti-rotavirus IgA testing, as was performed in the pre-licensure clinical efficacy trials, 49 and their geometric mean titer would add valuable information to assess the immune responses in infants with MRC. In summary, the RIVAR study population included more vulnerable infants with regard to gestational age, bir thweight and comorbidities, compared to other studies among specific risk populations ( table 1 ), which may explain the lower vaccine effectiveness. In addition, these studies were performed in settings with universal rotavirus vaccination, where herd protection potentially contributed to measured vaccine effects. To improve rotavirus vaccine performance among medical risk infants, alternative vaccination strategies should be explored. The novel parenteral rotavirus vaccines may offer a solution. 50 Vaccine responses to other parenteral childhood vaccinations were adequate in a subset of the prematurely born infants par ticipating in RIVAR. 51 Alternatively, the rotavirus vaccination schedule could be adapted to improve immune responses, for instance by adding a third dose for Rotarix or by changing intervals between dosing. Non-specific effects of vaccination For live-attenuated vaccines, some studies have repor ted beneficial non-specific effects.Trained immunity is the proposed mechanism by which live-attenuated vaccines enhance the innate immune response to subsequent and non-target infections. 52,53 The RIVAR study population would greatly benefit from such non-specific effects, as these infants are at increased risk of respiratory infections and hospitalizations. However, we did not find significant beneficial effects on hospitalization for non-target diseases or on incidence of acute respiratory infections after