IL-1β as mucosal vaccine adjuvant : the specific induction of tissue-resident memory T cells improves the heterosubtypic immunity against influenza A viruses
| Autor: | Rebecca Heß, Christina Ehrhardt, Matthias Tenbusch, V Heinecke, Viktoria Stab, M. Storcksdieck genannt Bonsmann, K Watzstedt, Wibke Bayer, Dennis Lapuente, Astrid M. Westendorf, André Maaske |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Influenza vaccine medicine.medical_treatment T cell T-Lymphocytes Immunology Genetic Vectors Interleukin-1beta Medizin Biology Antibodies Viral Immunity Heterologous Adenoviridae 03 medical and health sciences Mice Antigen Adjuvants Immunologic Orthomyxoviridae Infections Immunity Influenza Human medicine Immunology and Allergy Animals Humans Cells Cultured Heterosubtypic immunity Mice Inbred BALB C Immunogenicity Interleukin-18 Dendritic Cells Virology Antibodies Neutralizing 030104 developmental biology medicine.anatomical_structure Influenza A virus Influenza Vaccines Organ Specificity biology.protein Female Antibody Adjuvant Immunologic Memory |
| Popis: | 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)-1 beta or rAd-IL-18 were evaluated for their efficacy in BALB/c mice. Mucosal delivery of rAd-IL-1 beta 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(+)CD69(+) tissue-resident memory T cells (T-RM). 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-RM for the local containment of mucosal infections. The local co-expression of IL-1 beta and antigen lead to the activation of critical checkpoints in the formation of T-RM including activation of epithelial cells, expression of chemokines and adhesion molecules, recruitment of lung-derived CD103(+) DCs, and finally local T-RM imprinting. Given the importance of T-RM-mediated protection at mucosal barriers, this study has major implications for vaccine development. |
| Databáze: | OpenAIRE |
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