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

Scientific Reports
Karen E GoochMiles W Carroll

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.

References

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Nov 8, 2017·Proceedings of the National Academy of Sciences of the United States of America·Seth J ZostScott E Hensley

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Citations

Feb 20, 2020·American Journal of Physiology. Lung Cellular and Molecular Physiology·Jinghui GaoAmy L Ryan
Nov 2, 2019·Journal of Clinical Microbiology·Kuiama LewandowskiPhilippa C Matthews
Apr 12, 2020·Vaccines·Amanda L Skarlupka, Ted M Ross

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Methods Mentioned

BETA
ELISA
flow cytometry
enzyme-linked immunosorbent
chip
enzyme linked immunosorbent assay

Software Mentioned

SigmaPlot
GraphPad Prism

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