Intestinal helminth infection impairs vaccine-induced T cell responses and protection against SARS-CoV-2 in mice

Sci Transl Med. 2024 Aug 21;16(761):eado1941. doi: 10.1126/scitranslmed.ado1941. Epub 2024 Aug 21.

Abstract

Although vaccines have reduced the burden of COVID-19, their efficacy in helminth infection-endemic areas is not well characterized. We evaluated the impact of infection by Heligmosomoides polygyrus bakeri (Hpb), a murine intestinal roundworm, on the efficacy of an mRNA vaccine targeting the Wuhan-1 spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in mice. Although immunization generated similar B cell responses in Hpb-infected and uninfected mice, polyfunctional CD4+ and CD8+ T cell responses were markedly reduced in Hpb-infected mice. Hpb-infected and mRNA-vaccinated mice were protected against the ancestral SARS-CoV-2 strain WA1/2020, but control of lung infection was diminished against an Omicron variant compared with animals immunized without Hpb infection. Helminth-mediated suppression of spike protein-specific CD8+ T cell responses occurred independently of signal transducer and activator of transcription 6 (STAT6) signaling, whereas blockade of interleukin-10 (IL-10) rescued vaccine-induced CD8+ T cell responses. Together, these data show that, in mice, intestinal helminth infection impaired vaccine-induced T cell responses through an IL-10 pathway, which compromised protection against antigenically drifted SARS-CoV-2 variants.

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes* / immunology
  • COVID-19 Vaccines* / immunology
  • COVID-19* / immunology
  • COVID-19* / prevention & control
  • Female
  • Interleukin-10* / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Nematospiroides dubius* / immunology
  • SARS-CoV-2* / immunology
  • STAT6 Transcription Factor / metabolism
  • Spike Glycoprotein, Coronavirus / immunology
  • Strongylida Infections / immunology
  • T-Lymphocytes / immunology

Substances

  • COVID-19 Vaccines
  • Interleukin-10
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • STAT6 Transcription Factor

Supplementary concepts

  • SARS-CoV-2 variants