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Non-specific effects of a modified measles vaccination schedule to prevent allergy and unrelated infection in children

In addition to their specific effect against the target disease, some vaccines induce broader changes to immune function, resulting in “non-specific effects”. Evidence suggests that measles vaccines can protect against unrelated infections (not related to the measles virus) and reduce all-cause mortality by as much as half in infants. In two trials in Guinea-Bissau, an early dose of measles vaccine (before 9 months of age) was associated with reduced risk of hospital admission and of mild infections in the months following vaccination. Importantly, the non-specific effects are mainly observed when the measles-containing vaccine (such as the measles-mumps-rubella (MMR) vaccine) is not given concomitantly with non-live vaccines (such as the diphtheria-tetanus-pertussis vaccine). Measles vaccination has also been associated with a reduced risk of allergy in children. The overall objective of the funded project is to assess, in a randomised control trial (RCT), the effects of a “modified” MMR schedule in children, by an in-depth characterisation of both the clinical effects and the underlying immunomodulatory changes. The current Swiss administration schedule of giving MMR at 9 and 12 months of age (“current schedule”) will be compared with an optimised schedule. This is expected to maximise the beneficial non-specific effects of MMR by giving it at 6 and 13 months of age, separately from other vaccines (“modified schedule”). Factorial analysis will enable assessment of the benefit of the intervention on each of the two doses of MMR separately or in combination. Optimising the schedule of MMR vaccination might have significant indirect effects on children’s health; understanding the pathways involved in the non-specific effects of vaccines enable these effects to be exploited further, and has been postulated to save an additional one million deaths per year worldwide. This will be the first RCT to link clinical to immunological non-specific effects of MMR in children.