Vaccine-generated lung tissue-resident memory T cells provide heterosubtypic protection to influenza infection

JCI Insight. 2016 Jul 7;1(10):e85832. doi: 10.1172/jci.insight.85832.

Abstract

Tissue-resident memory T cells (TRM) are a recently defined, noncirculating subset with the potential for rapid in situ protective responses, although their generation and role in vaccine-mediated immune responses is unclear. Here, we assessed TRM generation and lung-localized protection following administration of currently licensed influenza vaccines, including injectable inactivated influenza virus (IIV, Fluzone) and i.n. administered live-attenuated influenza virus (LAIV, FluMist) vaccines. We found that, while IIV preferentially induced strain-specific neutralizing antibodies, LAIV generated lung-localized, virus-specific T cell responses. Moreover, LAIV but not IIV generated lung CD4+ TRM and virus-specific CD8+ TRM, similar in phenotype to those generated by influenza virus infection. Importantly, these vaccine-generated TRM mediated cross-strain protection, independent of circulating T cells and neutralizing antibodies, which persisted long-term after vaccination. Interestingly, intranasal administration of IIV or injection of LAIV failed to elicit T cell responses or provide protection against viral infection, demonstrating dual requirements for respiratory targeting and a live-attenuated strain to establish TRM. The ability of LAIV to generate lung TRM capable of providing long-term protection against nonvaccine viral strains, as demonstrated here, has important implications for protecting the population against emergent influenza pandemics by direct fortification of lung-specific immunity.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antibodies, Neutralizing / blood
  • Antibodies, Viral / blood
  • Female
  • Influenza Vaccines / therapeutic use*
  • Lung / cytology
  • Lung / immunology
  • Mice
  • Mice, Inbred C57BL
  • Orthomyxoviridae Infections / immunology*
  • T-Lymphocytes / immunology*
  • Vaccines, Attenuated / therapeutic use

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • FluMist
  • Fluzone High-Dose
  • Influenza Vaccines
  • Vaccines, Attenuated