Heterosubtypic cross-protection correlates with cross-reactive interferon-gamma-secreting lymphocytes in the ferret model of influenza

Sci Rep. 2019 Feb 22;9(1):2617. doi: 10.1038/s41598-019-38885-0.

Abstract

An effective universal vaccine for influenza will likely need to induce virus-specific T-cells, which are the major mediator of heterosubtypic cross-protection between different subtypes of influenza A virus. In this study we characterise the cell-mediated immune response in ferrets during heterosubtypic protection induced by low-dose H1N1 virus infection against an H3N2 virus challenge, given 4 weeks later. Although the ferrets were not protected against the infection by H3N2 virus, the duration of virus shedding was shortened, and clinical disease was markedly reduced. No cross-reactive neutralizing antibodies were detected, but cross-reactive interferon-gamma-secreting T cells were detected in the circulation prior to H3N2 challenge. These T-cells peaked at 11 days post-H1N1 infection, and were strongly induced in blood and in lung following H3N2 infection. The rapid induction of interferon-gamma-secreting cells in ferrets previously infected with H1N1 virus, but not in naïve ferrets, suggests induction of memory T-cells. These results are in accord with the observations that pre-existing cross-reactive T-cells correlate with protection in humans and have implications for outbreak modelling and universal vaccine design.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibody Formation / immunology
  • Cell Count
  • Cross Protection / immunology*
  • Cross Reactions / immunology*
  • Disease Models, Animal
  • Dogs
  • Dose-Response Relationship, Immunologic
  • Female
  • Ferrets / immunology*
  • Ferrets / virology*
  • Immunity, Humoral
  • Inflammation / immunology
  • Inflammation / pathology
  • Influenza A Virus, H1N1 Subtype / immunology
  • Influenza A Virus, H3N2 Subtype / immunology
  • Interferon-gamma / metabolism*
  • Lymphocytes / immunology*
  • Madin Darby Canine Kidney Cells
  • Orthomyxoviridae Infections / immunology*
  • Orthomyxoviridae Infections / veterinary*

Substances

  • Interferon-gamma