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Journal of Virology, June 2001, p. 5036-5042, Vol. 75, No. 11
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.11.5036-5042.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Coadministration of Gamma Interferon with DNA Vaccine Expressing Woodchuck Hepatitis Virus (WHV) Core Antigen Enhances the Specific Immune Response and Protects against WHV Infection

Felix Siegel, Mengji Lu, and Michael Roggendorf*

Institut für Virologie, Universitätsklinikum Essen, Essen, Germany

Received 4 December 2000/Accepted 5 March 2001

DNA vaccinations are able to induce strong cellular immune responses in mice and confer protection against infectious agents. However, DNA vaccination of large animals appears to be less effective and requires repeated injections of large amounts of plasmid DNA. Enhancement of the efficiency of DNA vaccines may be achieved by coapplication of cytokine-expressing plasmids. Here we investigated, with woodchucks, whether coadministration of an expression plasmid for woodchuck gamma interferon (IFN-gamma ), pWIFN-gamma , can improve DNA vaccination with woodchuck hepatitis virus core antigen (WHcAg). Animals were immunized with pWHcIm (a plasmid expressing WHcAg) alone or with a combination of pWHcIm and pWIFN-gamma using a gene gun. Six weeks postimmunization, all animals were challenged with 105 genome equivalents of woodchuck hepatitis virus (WHV). The antibody and lymphoproliferative immune responses to WHV proteins were determined after immunization and after challenge. Vaccination with pWHcIm and pWIFN-gamma led to a pronounced lymphoproliferative response to WHcAg and protected woodchucks against subsequent virus challenge. Two of three animals vaccinated with pWHcIm alone did not show a detectable lymphoproliferative response to WHcAg. A low-level WHV infection occurred in these woodchucks after challenge, as WHV DNA was detectable in the serum by PCR. None of the pWHcIm-vaccinated animals showed an anti-WHcAg antibody response after DNA vaccination or an anamnestic response after virus challenge. Our results indicate that coadministration of the WIFN-gamma gene with pWHcIm enhanced the specific cellular immune response and improved the protective efficacy of WHV-specific DNA vaccines.


* Corresponding author. Mailing address: Institut für Virologie, Universitätsklinikum Essen, Hufelandstrasse 55, 45122 Essen, Germany. Phone: 49 201 723 3550. Fax: 49 201 723 5929. E-mail: roggendorf{at}uni-essen.de.


Journal of Virology, June 2001, p. 5036-5042, Vol. 75, No. 11
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.11.5036-5042.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.



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