[HTML][HTML] Vaccine-generated lung tissue–resident memory T cells provide heterosubtypic protection to influenza infection

KD Zens, JK Chen, DL Farber - JCI insight, 2016 - ncbi.nlm.nih.gov
KD Zens, JK Chen, DL Farber
JCI insight, 2016ncbi.nlm.nih.gov
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 in administered live-
attenuated influenza virus (LAIV, FluMist) vaccines. We found that, while IIV preferentially …
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 in 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.
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