tetano
Editor, Senior Moderator
Mucosal Immunol. 2018 Mar 15. doi: 10.1038/s41385-018-0017-4. [Epub ahead of print]
[h=1]IL-1β as mucosal vaccine adjuvant: the specific induction of tissue-resident memory T cells improves the heterosubtypic immunity against influenza A viruses.[/h] Lapuente D[SUP]1,[/SUP][SUP]2[/SUP], Storcksdieck Genannt Bonsmann M[SUP]1[/SUP], Maaske A[SUP]1[/SUP], Stab V[SUP]1[/SUP], Heinecke V[SUP]1[/SUP], Watzstedt K[SUP]1[/SUP], He? R[SUP]1[/SUP], Westendorf AM[SUP]3[/SUP], Bayer W[SUP]4[/SUP], Ehrhardt C[SUP]5[/SUP], Tenbusch M[SUP]6,[/SUP][SUP]7[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] A universal influenza vaccine must provide protection against antigenically divergent influenza viruses either through broadly neutralizing antibodies or cross-reactive T cells. Here, intranasal immunizations with recombinant adenoviral vectors (rAd) encoding hemagglutinin (HA) and nucleoprotein (NP) in combination with rAd-Interleukin-(IL)-1β or rAd-IL-18 were evaluated for their efficacy in BALB/c mice. Mucosal delivery of rAd-IL-1β enhanced HA-specific antibody responses including strain-specific neutralizing antibodies. Nevertheless, the beneficial effects on the local T cell responses were much more impressive reflected by increased numbers of CD103[SUP]+[/SUP]CD69[SUP]+[/SUP] tissue-resident memory T cells (T[SUB]RM[/SUB]). This increased immunogenicity translated into superior protection against infections with homologous and heterologous strains including H1N1, pH1N1, H3N2, and H7N7. Inhibition of the egress of circulating T cells out of the lymph nodes during the heterologous infection had no impact on the degree of protection underscoring the unique potential of T[SUB]RM[/SUB] for the local containment of mucosal infections. The local co-expression of IL-1β and antigen lead to the activation of critical checkpoints in the formation of T[SUB]RM[/SUB] including activation of epithelial cells, expression of chemokines and adhesion molecules, recruitment of lung-derived CD103[SUP]+[/SUP] DCs, and finally local T[SUB]RM[/SUB] imprinting. Given the importance of T[SUB]RM[/SUB]-mediated protection at mucosal barriers, this study has major implications for vaccine development.
PMID: 29545648 DOI: 10.1038/s41385-018-0017-4
[h=1]IL-1β as mucosal vaccine adjuvant: the specific induction of tissue-resident memory T cells improves the heterosubtypic immunity against influenza A viruses.[/h] Lapuente D[SUP]1,[/SUP][SUP]2[/SUP], Storcksdieck Genannt Bonsmann M[SUP]1[/SUP], Maaske A[SUP]1[/SUP], Stab V[SUP]1[/SUP], Heinecke V[SUP]1[/SUP], Watzstedt K[SUP]1[/SUP], He? R[SUP]1[/SUP], Westendorf AM[SUP]3[/SUP], Bayer W[SUP]4[/SUP], Ehrhardt C[SUP]5[/SUP], Tenbusch M[SUP]6,[/SUP][SUP]7[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] A universal influenza vaccine must provide protection against antigenically divergent influenza viruses either through broadly neutralizing antibodies or cross-reactive T cells. Here, intranasal immunizations with recombinant adenoviral vectors (rAd) encoding hemagglutinin (HA) and nucleoprotein (NP) in combination with rAd-Interleukin-(IL)-1β or rAd-IL-18 were evaluated for their efficacy in BALB/c mice. Mucosal delivery of rAd-IL-1β enhanced HA-specific antibody responses including strain-specific neutralizing antibodies. Nevertheless, the beneficial effects on the local T cell responses were much more impressive reflected by increased numbers of CD103[SUP]+[/SUP]CD69[SUP]+[/SUP] tissue-resident memory T cells (T[SUB]RM[/SUB]). This increased immunogenicity translated into superior protection against infections with homologous and heterologous strains including H1N1, pH1N1, H3N2, and H7N7. Inhibition of the egress of circulating T cells out of the lymph nodes during the heterologous infection had no impact on the degree of protection underscoring the unique potential of T[SUB]RM[/SUB] for the local containment of mucosal infections. The local co-expression of IL-1β and antigen lead to the activation of critical checkpoints in the formation of T[SUB]RM[/SUB] including activation of epithelial cells, expression of chemokines and adhesion molecules, recruitment of lung-derived CD103[SUP]+[/SUP] DCs, and finally local T[SUB]RM[/SUB] imprinting. Given the importance of T[SUB]RM[/SUB]-mediated protection at mucosal barriers, this study has major implications for vaccine development.
PMID: 29545648 DOI: 10.1038/s41385-018-0017-4