Authors
S Babayan2; S Venkatesan1; E Smith2; A Sweeny1; J Hall2; AB Pedersen1; 1 Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, UK; 2 School of Biodiversity, One Health, and Veterinary Medicine, University of Glasgow, Glasgow, UK Discussion
Individuals vary substantially in their responses to vaccination due to a range of factors that include intrinsic host factors such as age, sex, and genetics, and acquired extrinsic factors such as pre-existing adaptive immunity, microbiota, and infections. The evidence for how parasitic helminths in particular might affect vaccine responsiveness is mixed, with some studies showing a range of effects from enhancement to suppression. Various factors, such as vaccine type and route of administration, the presence of distinct parasite species and the ability of helminths to alter the immune system, microbiota composition, and gut epithelium, have been cited as possible explanations for such apparent inconsistency. Yet issues with quantitative methods can also confound the interpretation of vaccine responses, leading to apparently contradictory effects of helminths on vaccine responses. Here, we present a causal analysis of the drivers and downstream effects of variation in helminth infection with respect to vaccine responsiveness using a paired laboratory-wild rodent system in which we manipulated diet and habitat. We found that under standard (and thus potentially confounded) analysis, helminth infection appeared to be associated with reduced vaccine responsiveness. However, in a causally explicit model where confounding was accounted for, we found no evidence that helminth infection was associated with reduced vaccine responsiveness. We also found that diet, sex, and reproductive status had negligible effects on parasite burdens in this set of experiments. These results suggest that while immunity to helminths and vaccine responsiveness may be context dependant, parasite burdens themselves may not be a direct driver of variation in vaccine responses. 
