Rotavirus vaccine efficacy: current status and areas for improvement

Carvalho, Miguel F.; Gill, Davinder

The difference in Rotavirus vaccine efficacy noted between high and low-income countries indicates that novel, more appropriate and effective vaccines should be developed to address the specific requirements of the populations that need them the most. Currently, there are knowledge gaps in mucosal immunity and its response to Rotavirus infection. Increasing our understanding in this area, especially among young children, would likely provide critical insights. There is also little information on the role of circadian rhythms in vaccine response and more studies, specially addressing mucosal immunity, are needed. It is however known that in pre-clinical models, virus infection is affected and also that for instance the expression of critical pattern-recognition receptors associated with responses to pathogen such as TLRs (including in intestinal tissue) depends on circadian rhythms. 121, 123 In order to address these current gaps in knowledge, performing an integrative systems vaccinology 'omics' analysis 102 of intestinal mucosal immunity with healthy humans of various ages and ethnic/genetic backgrounds, before and after (Rotavirus) vaccination, could prove informative. This would comprise also an evaluation of circadian patterns of expression, including genes associated with pathogen entry. The study could then be extended to individuals affected by different levels of entheropathy from matching age/ethnic/ genetic backgrounds. Analysing outputs could provide new venues for intervention to compensate for defects in critical pathways relating to e.g. pathogen entry and immune responses that are affected in sick individuals. Simple solutions such as using pertinent adjuvants, as well as timely provision of supplements and possibly also sourcing locally available food and remedies. In addition, circadian gene expression patterns would potentially give indications on whether vaccine administration at specific times of day could contribute to a higher efficacy.