Abstract
Following the introduction of live-attenuated rotavirus vaccines in many countries, a notable reduction in deaths and hospitalisations associated with diarrhoea in children <5 years of age has been reported. There is growing evidence to suggest that live-attenuated vaccines also provide protection against other infections beyond the vaccine-targeted pathogens. These so called off-target effects of vaccination have been associated with the tuberculosis vaccine Bacille Calmette Guérin (BCG), measles, oral polio and recently salmonella vaccines, and are thought to be mediated by modified innate and possibly adaptive immunity. Indeed, rotavirus vaccines have been reported to provide greater than expected reductions in acute gastroenteritis caused by other enteropathogens, that have mostly been attributed to herd protection and prior underestimation of rotavirus disease. Whether rotavirus vaccines also alter the immune system to reduce non targeted gastrointestinal infections has not been studied directly. Here we review the current understanding of the mechanisms underlying off-target effects of vaccines and propose a mechanism by which the live-attenuated neonatal rotavirus vaccine, RV3-BB, could promote protection beyond the targeted pathogen. Finally, we consider how vaccine developers may leverage these properties to improve health outcomes in children, particularly those in low-income countries where disease burden and mortality is disproportionately high relative to developed countries.
Highlights
Diarrhoea, pneumonia and malaria remain the leading causes of death among children under the age of five years [1]
Diarrhoeal disease associated with rotavirus infection accounts for an estimated 128,500 under-five deaths annually, despite increasing rollout of rotavirus vaccines [2,3]
Observational studies conducted in both high income and middle-income settings suggest that rotavirus vaccines may provide protection against severe acute gastroenteritis not associated with rotavirus [8–10]
Summary
Pneumonia and malaria remain the leading causes of death among children under the age of five years [1]. Further understanding of the mechanisms through which new and existing vaccines induce broad-based immunity against a range of pathogens would be of considerable value to high disease-burdened regions. Both epidemiological and immunological studies suggest that certain vaccines exhibit immuno-modulatory functions that induce beneficial off-target effects against unrelated pathogens. Strong evidence on non-specific effects has been reported from live-attenuated vaccines, notably Bacille Calmette Guérin (BCG) and measles vaccines [11–14]. It is uncertain whether similar effects are applicable to rotavirus vaccines. We postulate that live-attenuated rotavirus vaccines administered orally at birth might induce beneficial non-specific effects, and confer protection to unrelated pathogens, and have reviewed the available literature in this area
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