Pre-existing helminth infection impairs the efficacy of adjuvanted influenza vaccination in mice

PLoS One. 2022 Mar 31;17(3):e0266456. doi: 10.1371/journal.pone.0266456. eCollection 2022.

Abstract

The world health organization estimates that more than a quarter of the human population is infected with parasitic worms that are called helminths. Many helminths suppress the immune system of their hosts to prolong their survival. This helminth-induced immunosuppression "spills over" to unrelated antigens and can suppress the immune response to vaccination against other pathogens. Indeed, several human studies have reported a negative correlation between helminth infections and responses to vaccinations. Using mice that are infected with the parasitic nematode Litomosoides sigmodontis as a model for chronic human filarial infections, we reported previously that concurrent helminth infection impaired the vaccination-induced protection against the human pathogenic 2009 pandemic H1N1 influenza A virus (2009 pH1N1). Vaccinated, helminth-infected mice produced less neutralizing, influenza-specific antibodies than vaccinated naïve control mice. Consequently helminth-infected and vaccinated mice were not protected against a challenge infection with influenza virus but displayed high virus burden in the lung and a transient weight loss. In the current study we tried to improve the vaccination efficacy using vaccines that are licensed for humans. We either introduced a prime-boost vaccination regimen using the non-adjuvanted anti-influenza vaccine Begripal or employed the adjuvanted influenza vaccine Fluad. Although both strategies elevated the production of influenza-specific antibodies and protected mice from the transient weight loss that is caused by an influenza challenge infection, sterile immunity was not achieved. Helminth-infected vaccinated mice still had high virus burden in the lung while non-helminth-infected vaccinated mice rapidly cleared the virus. In summary we demonstrate that basic improvements of influenza vaccination regimen are not sufficient to confer sterile immunity on the background of helminth-induced immunosuppression, despite amelioration of pathology i.e. weight loss. Our findings highlight the risk of failed vaccinations in helminth-endemic areas, especially in light of the ongoing vaccination campaign to control the COVID-19 pandemic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic
  • Animals
  • Antibodies, Viral
  • COVID-19*
  • Helminthiasis*
  • Helminths*
  • Humans
  • Influenza A Virus, H1N1 Subtype*
  • Influenza A virus*
  • Influenza Vaccines*
  • Influenza, Human* / complications
  • Influenza, Human* / prevention & control
  • Mice
  • Orthomyxoviridae Infections*
  • Pandemics
  • Vaccination
  • Weight Loss

Substances

  • Adjuvants, Immunologic
  • Antibodies, Viral
  • Influenza Vaccines

Grants and funding

MB was supported by the German Research Association DFG (https://www.dfg.de/) project 3754/ 2-1 /2-2. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.