IKKβ‐induced inflammation impacts the kinetics but not the magnitude of the immune response to a viral vector

• Published in: European journal of immunology Vol. 42; no. 3; pp. 681 - 687
• Main Authors: Hopewell, Emily L., Bronk, Crystina C., Massengill, Michael, Engelman, Robert W., Beg, Amer A.
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY‐VCH Verlag 01.03.2012
• Subjects: Adaptive Immunity - immunology; Adenoviridae - genetics; Adenoviridae - immunology; Adjuvants; Adjuvants, Immunologic - pharmacology; Animals; DCs; Genetic Vectors - genetics; Genetic Vectors - immunology; I-kappa B Kinase - immunology; IKKβ; Immunization - standards; Kinetics; Lung - immunology; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; NF-kappa B - immunology; NF‐κB; Specific Pathogen-Free Organisms
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.201141910

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/NF‐κB 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.