tetano
Editor, Senior Moderator
JCI Insight. 2016 Jul 7;1(10). pii: e85832.
[h=1]Vaccine-generated lung tissue-resident memory T cells provide heterosubtypic protection to influenza infection.[/h] Zens KD[SUP]1[/SUP], Chen JK[SUP]2[/SUP], Farber DL[SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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[SUP]+[/SUP] TRM and virus-specific CD8[SUP]+[/SUP] 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.
PMID: 27468427 DOI: 10.1172/jci.insight.85832
[PubMed]
[h=1]Vaccine-generated lung tissue-resident memory T cells provide heterosubtypic protection to influenza infection.[/h] Zens KD[SUP]1[/SUP], Chen JK[SUP]2[/SUP], Farber DL[SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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[SUP]+[/SUP] TRM and virus-specific CD8[SUP]+[/SUP] 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.
PMID: 27468427 DOI: 10.1172/jci.insight.85832
[PubMed]