title: IKKβ-induced inflammation impacts the kinetics but not the magnitude of the immune response to a viral vector.
abstract: Microbial adjuvants in vaccines activate key transcription factors, including NF-κB and interferon response factors (IRFs). However, the individual role of these transcription factor pathways in promoting adaptive immunity by adjuvants is not clear. It is widely believed that induction of a strong inflammatory response potentiates an adaptive immune response. In this study, we sought to determine whether activation of the pro-inflammatory inhibitor of κB kinase β (IKKβ) canonical NF-κB pathway promoted vaccine-induced immune responses. An adenovirus expressing constitutively activated IKKβ (AdIKK) induced robust DC maturation and high expression of key cytokines compared with a control virus. In vivo, AdIKK triggered rapid inflammation after pulmonary infection, increased leukocyte entry into draining LNs, and enhanced early antibody and T-cell responses. Notably, AdIKK did not influence the overall magnitude of the adaptive immune response. These results indicate that induction of inflammation by IKKβ/NFκB in this setting impacts the kinetics but not the magnitude of adaptive immune responses. These findings therefore help define the individual role of a key pathway induced by vaccine adjuvants in promoting adaptive immunity.
authors.affiliation: Moffitt Cancer Center, Department of Immunology, 12902 Magnolia Drive, Tampa, FL 33612, USA.
authors.forename: Emily L
authors.initials: EL
authors.lastname: Hopewell
authors.forename: Crystina C
authors.initials: CC
authors.lastname: Bronk
authors.forename: Michael
authors.initials: M
authors.lastname: Massengill
authors.forename: Robert W
authors.initials: RW
authors.lastname: Engelman
authors.forename: Amer A
authors.initials: AA
authors.lastname: Beg
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology*; D000256:Adenoviridae / Q000235:genetics / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D005822:Genetic Vectors / Q000235:genetics / Q000276:immunology; D051550:I-kappa B Kinase / Q000276:immunology*; D007114:Immunization / Q000592:standards*; D007700:Kinetics; D008168:Lung / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000276:immunology*; D013047:Specific Pathogen-Free Organisms
chemical_list: D000276:Adjuvants, Immunologic; D016328:NF-kappa B; D051550:I-kappa B Kinase