title: Vaccine-generated lung tissue-resident memory T cells provide heterosubtypic protection to influenza infection.
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.
authors.affiliation: Columbia Center for Translational Immunology.|Department of Microbiology and Immunology, and.
authors.forename: Kyra D
authors.initials: KD
authors.lastname: Zens
authors.affiliation: Columbia Center for Translational Immunology.
authors.forename: Jun Kui
authors.initials: JK
authors.lastname: Chen
authors.affiliation: Columbia Center for Translational Immunology.|Department of Microbiology and Immunology, and.|Department of Surgery, Columbia University Medical Center (CUMC), New York, New York, USA.
authors.forename: Donna L
authors.initials: DL
authors.lastname: Farber
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D005260:Female; D007252:Influenza Vaccines / Q000627:therapeutic use*; D008168:Lung / Q000166:cytology / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000627:therapeutic use
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; C000613429:FluMist; C000618615:Fluzone High-Dose; D007252:Influenza Vaccines; D014613:Vaccines, Attenuated