Interleukin-1 Family Cytokines as Mucosal Vaccine Adjuvants for Induction of Protective Immunity against Influenza Virus
Open Access
- 15 December 2010
- journal article
- research article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 84 (24), 12703-12712
- https://doi.org/10.1128/jvi.01182-10
Abstract
A safe and potent adjuvant is needed for development of mucosal vaccines against etiological agents, such as influenza virus, that enter the host at mucosal surfaces. Cytokines are potential adjuvants for mucosal vaccines because they can enhance primary and memory immune responses enough to protect against some infectious agents. For this study, we tested 26 interleukin (IL) cytokines as mucosal vaccine adjuvants and compared their abilities to induce antigen (Ag)-specific immune responses against influenza virus. In mice intranasally immunized with recombinant influenza virus hemagglutinin (rHA) plus one of the IL cytokines, IL-1 family cytokines (i.e., IL-1α, IL-1β, IL-18, and IL-33) were found to increase Ag-specific immunoglobulin G (IgG) in plasma and IgA in mucosal secretions compared to those after immunization with rHA alone. In addition, high levels of both Th1- and Th2-type cytokines were observed in mice immunized with rHA plus an IL-1 family cytokine. Furthermore, mice intranasally immunized with rHA plus an IL-1 family cytokine had significant protection against a lethal influenza virus infection. Interestingly, the adjuvant effects of IL-18 and IL-33 were significantly decreased in mast cell-deficient W/W v mice, indicating that mast cells have an important role in induction of Ag-specific mucosal immune responses induced by IL-1 family cytokines. In summary, our results demonstrate that IL-1 family cytokines are potential mucosal vaccine adjuvants and can induce Ag-specific immune responses for protection against pathogens like influenza virus.Keywords
This publication has 49 references indexed in Scilit:
- Mast Cell-Mediated Antigen Presentation Regulates CD8+ T Cell Effector FunctionsImmunity, 2009
- TNF superfamily member, TL1A, is a potential mucosal vaccine adjuvantBiochemical and Biophysical Research Communications, 2009
- Immunological and Inflammatory Functions of the Interleukin-1 FamilyAnnual Review of Immunology, 2009
- The role of TNF superfamily members in T-cell function and diseasesNature Reviews Immunology, 2009
- Homeostasis of Naive and Memory T CellsImmunity, 2008
- Functional CD8+ CTLs in mucosal sites and HIV infection: moving forward toward a mucosal AIDS vaccineTrends in Immunology, 2008
- Critical issues in mucosal immunity for HIV-1 vaccine developmentJournal of Allergy and Clinical Immunology, 2008
- TANK-binding kinase-1 delineates innate and adaptive immune responses to DNA vaccinesNature, 2008
- Vaccines and VaccinationThe New England Journal of Medicine, 2001
- Natural killer cells, viruses and cancerNature Reviews Immunology, 2001