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Journal of Virology, October 2007, p. 10606-10613, Vol. 81, No. 19
0022-538X/07/$08.00+0     doi:10.1128/JVI.01000-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Effects of Type I Interferons on the Adjuvant Properties of Plasmid Granulocyte-Macrophage Colony-Stimulating Factor In Vivo{triangledown}

Lizeng Qin, John R. Greenland, Chikaya Moriya, Mark J. Cayabyab, and Norman L. Letvin*

Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115

Received 8 May 2007/ Accepted 13 July 2007

While administration of granulocyte-macrophage colony-stimulating factor (GM-CSF) can induce the local recruitment of activated antigen-presenting cells at the site of vaccine inoculation, this cellular recruitment is associated with a paradoxical decrease in local vaccine antigen expression and vaccine-elicited CD8+ T-cell responses. To clarify why this cytokine administration does not potentiate immunization, we examined the recruited cells and expressed inflammatory mediators in muscles following intramuscular administration of plasmid GM-CSF in mice. While large numbers of dendritic cells and macrophages were attracted to the site of plasmid GM-CSF inoculation, high concentrations of type I interferons were also detected in the muscles. As type I interferons have been reported to damp foreign gene expression in vivo, we examined the possibility that these local innate mediators might decrease plasmid DNA expression and therefore the immunogenicity of plasmid DNA vaccines. In fact, we found that coadministration of an anti-beta interferon monoclonal antibody with the plasmid DNA immunogen and plasmid GM-CSF restored both the local antigen expression and the CD8+ T-cell immunogenicity of the vaccine. These data demonstrate that local innate immune responses can change the ability of vaccines to generate robust adaptive immunity.

* Corresponding author. Mailing address: Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave., Boston, MA 02215. Phone: (617) 667-2766. Fax: (617) 667-8210. E-mail: nletvin{at}bidmc.harvard.edu

{triangledown} Published ahead of print on 25 July 2007.

Journal of Virology, October 2007, p. 10606-10613, Vol. 81, No. 19
0022-538X/07/$08.00+0     doi:10.1128/JVI.01000-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.





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