Harnessing alveolar macrophages for sustained mucosal T-cell recall confers long-term protection to mice against lethal influenza challenge without clinical disease

Mucosal Immunol. 2014 Jan;7(1):89-100. doi: 10.1038/mi.2013.27. Epub 2013 May 29.


Vaccines that induce T cells, which recognize conserved viral proteins, could confer universal protection against seasonal and pandemic influenza strains. An effective vaccine should generate sufficient mucosal T cells to ensure rapid viral control before clinical disease. However, T cells may also cause lung injury in influenza, so this approach carries inherent risks. Here we describe intranasal immunization of mice with a lentiviral vector expressing influenza nucleoprotein (NP), together with an NFκB activator, which transduces over 75% of alveolar macrophages (AM). This strategy recalls and expands NP-specific CD8+ T cells in the lung and airway of mice that have been immunized subcutaneously, or previously exposed to influenza. Granzyme B-high, lung-resident T-cell populations persist for at least 4 months and can control a lethal influenza challenge without harmful cytokine responses, weight loss, or lung injury. These data demonstrate that AM can be harnessed as effective antigen-presenting cells for influenza vaccination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Line
  • Cross Reactions / immunology
  • Cytokines / biosynthesis
  • Epitopes, T-Lymphocyte / immunology
  • Female
  • Gene Expression
  • Gene Order
  • Genetic Vectors / administration & dosage
  • Genetic Vectors / genetics
  • Humans
  • Immunization
  • Immunization, Secondary
  • Immunologic Memory*
  • Influenza A Virus, H1N1 Subtype / immunology
  • Influenza A virus / immunology*
  • Lentivirus / genetics
  • Lung / immunology
  • Lung / metabolism
  • Lung / pathology
  • Lung / virology
  • Macrophages, Alveolar / immunology*
  • Macrophages, Alveolar / metabolism
  • Mice
  • Orthomyxoviridae Infections / immunology*
  • Orthomyxoviridae Infections / mortality
  • Orthomyxoviridae Infections / therapy
  • Respiratory Mucosa / immunology*
  • Respiratory Mucosa / metabolism
  • T-Lymphocytes / immunology*
  • Transduction, Genetic
  • Transgenes
  • Virus Replication / immunology


  • Cytokines
  • Epitopes, T-Lymphocyte