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Journal of Virology, August 2003, p. 8729-8735, Vol. 77, No. 16
0022-538X/03/$08.00+0 DOI: 10.1128/JVI.77.16.8729-8735.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
Plasmid Chemokines and Colony-Stimulating Factors Enhance the Immunogenicity of DNA Priming-Viral Vector Boosting Human Immunodeficiency Virus Type 1 Vaccines
Dan H. Barouch,1* Paul F. McKay,1 Shawn M. Sumida,1 Sampa Santra,1 Shawn S. Jackson,1 Darci A. Gorgone,1 Michelle A. Lifton,1 Bimal K. Chakrabarti,2 Ling Xu,2 Gary J. Nabel,2 and Norman L. Letvin1
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215,1
Vaccine Research Center, National Institutes of Health, Bethesda, Maryland 208922
Received 19 March 2003/
Accepted 28 May 2003
Heterologous "prime-boost" regimens that involve priming with plasmid DNA vaccines and boosting with recombinant viral vectors have been shown to elicit potent virus-specific cytotoxic T-lymphocyte responses. Increasing evidence, however, suggests that the utility of recombinant viral vectors in human populations will be significantly limited by preexisting antivector immunity. Here we demonstrate that the coadministration of plasmid chemokines and colony-stimulating factors with plasmid DNA vaccines markedly increases the immunogenicity of DNA prime-recombinant adenovirus serotype 5 (rAd5) boost and DNA prime-recombinant vaccinia virus (rVac) boost vaccine regimens in BALB/c mice. In mice with preexisting anti-Ad5 immunity, priming with the DNA vaccine alone followed by rAd5 boosting elicited only marginal immune responses. In contrast, cytokine-augmented DNA vaccine priming followed by rAd5 vector boosting was able to generate potent immune responses in mice with preexisting anti-Ad5 immunity. These data demonstrate that plasmid cytokines can markedly improve the immunogenicity of DNA prime-viral vector boost vaccine strategies and can partially compensate for antivector immunity.
* Corresponding author. Mailing address: Research East Rm. 113, Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, 330 Brookline Ave., Boston, MA 02215. Phone: (617) 667-4434. Fax: (617) 667-8210. E-mail:
dbarouch{at}bidmc.harvard.edu.
Journal of Virology, August 2003, p. 8729-8735, Vol. 77, No. 16
0022-538X/03/$08.00+0 DOI: 10.1128/JVI.77.16.8729-8735.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
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