Helminth Infections Suppress the Efficacy of Vaccination against Seasonal Influenza

Cell Rep. 2019 Nov 19;29(8):2243-2256.e4. doi: 10.1016/j.celrep.2019.10.051.

Abstract

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.

Keywords: Foxp3(+) regulatory T cells; Litomosoides sigmodontis; antibody response; helminth; immunomodulation; influenza; interleukin-10; parasite infection; type 1 regulatory T cells; vaccination efficacy.

MeSH terms

  • Animals
  • Antibody Formation / genetics
  • Antibody Formation / physiology
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism*
  • Helminths / immunology*
  • Helminths / pathogenicity*
  • Humans
  • Immunomodulation / immunology
  • Influenza A Virus, H1N1 Subtype / immunology
  • Influenza A Virus, H1N1 Subtype / pathogenicity*
  • Influenza Vaccines / therapeutic use
  • Influenza, Human / immunology
  • Influenza, Human / prevention & control*
  • Interleukin-10 / metabolism
  • Mice
  • Seasons
  • T-Lymphocytes / metabolism*
  • Vaccination / methods*

Substances

  • Forkhead Transcription Factors
  • Influenza Vaccines
  • Interleukin-10