Helminth Infections Suppress the Efficacy of Vaccination against Seasonal Influenza

Abstract

Summary: Helminth parasites infect more than a quarter of the human population and inflict significant changes to the immunological status of their hosts. Here, we analyze the impact of helminth infections on the efficacy of vaccinations using Litomosoides sigmodontis-infected mice. Concurrent helminth infection reduces the quantity and quality of antibody responses to vaccination against seasonal influenza. Vaccination-induced protection against challenge infections with the human pathogenic 2009 pandemic H1N1 influenza A virus is drastically impaired in helminth-infected mice. Impaired responses are also observed if vaccinations are performed after clearance of a previous helminth infection, suggesting that individuals in helminth-endemic areas may not always benefit from vaccinations, even in the absence of an acute and diagnosable helminth infection. Mechanistically, the suppression is associated with a systemic and sustained expansion of interleukin (IL)-10-producing CD4+CD49+LAG-3+ type 1 regulatory T cells and partially abrogated by in vivo blockade of the IL-10 receptor. : Parasitic worms down-modulate the immune system of their host to establish chronic infections. Hartmann et al. demonstrate that this suppresses responsiveness to vaccinations against influenza. Mice with on-going or previously resolved helminth infections displayed a systemic increase of Tr1 cells and impaired vaccination efficacy that was partially mediated by IL-10. Keywords: antibody response, Foxp3+ regulatory T cells, helminth, immunomodulation, influenza, interleukin-10, Litomosoides sigmodontis, parasite infection, type 1 regulatory T cells, vaccination efficacy