title: Type I interferon inhibits antibody responses induced by a chimpanzee adenovirus vector.
abstract: Recent studies have indicated that type I interferon (IFN) enhances antibody responses and promotes isotype switching. In this study, we analyzed the role of type I IFN signaling during the generation of transgene product-specific antibody responses elicited by recombinant adenovirus (Ad) vectors. A vector derived from a human Ad serotype (AdHu5) induced low levels of type I IFN following infection of dendritic cells (DCs) and stimulated normal transgene product-specific antibody responses in mice that have a defective type I IFN receptor (IFNAR(-/-)). A vector derived from a chimpanzee Ad serotype (AdC68) induced very high levels of type I IFN following infection of DCs, and surprisingly, primed stronger transgene product-specific antibody responses in IFNAR(-/-) mice compared to wild-type mice. The increased antibody response in IFNAR(-/-) mice vaccinated with the AdC68 vector was mainly due to the generation of IgG1 antibodies that were not elicited in wild-type mice. The induction of IgG1 antibodies correlated with an increase in transgene product expression in IFNAR(-/-) mice and was not associated with an increase in T helper 2 responses. We conclude that type I IFN, when induced at high levels, can downregulate transgene product expression of Ad vectors and inhibit the formation of optimal antibody responses.
authors.affiliation: Cell and Molecular Biology Group, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Scott E
authors.initials: SE
authors.lastname: Hensley
authors.forename: Ann S
authors.initials: AS
authors.lastname: Cun
authors.forename: Wynetta
authors.initials: W
authors.lastname: Giles-Davis
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Zhiquan
authors.initials: Z
authors.lastname: Xiang
authors.forename: Marcio O
authors.initials: MO
authors.lastname: Lasaro
authors.forename: Bryan R G
authors.initials: BR
authors.lastname: Williams
authors.forename: Robert H
authors.initials: RH
authors.lastname: Silverman
authors.forename: Hildegund C J
authors.initials: HC
authors.lastname: Ertl
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007370:Interferon Type I / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D002679:Pan troglodytes / Q000821:virology*; D053633:Receptor, Interferon alpha-beta / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D016207:Cytokines; D007074:Immunoglobulin G; D007370:Interferon Type I; D053633:Receptor, Interferon alpha-beta