Type I interferon inhibits antibody responses induced by a chimpanzee adenovirus vector

Mol Ther. 2007 Feb;15(2):393-403. doi: 10.1038/sj.mt.6300024.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenoviridae / genetics*
  • Animals
  • Bone Marrow Cells / immunology
  • Cytokines / metabolism
  • Dendritic Cells / immunology
  • Enzyme-Linked Immunosorbent Assay
  • Genetic Vectors / genetics*
  • Humans
  • Immunoglobulin G / immunology
  • Interferon Type I / genetics
  • Interferon Type I / metabolism
  • Interferon Type I / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Pan troglodytes / virology*
  • Receptor, Interferon alpha-beta / genetics
  • Receptor, Interferon alpha-beta / physiology
  • Signal Transduction / physiology
  • Th2 Cells / immunology


  • Cytokines
  • Immunoglobulin G
  • Interferon Type I
  • Receptor, Interferon alpha-beta