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Journal of Virology, July 2002, p. 6568-6576, Vol. 76, No. 13
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.13.6568-6576.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Induction of CD8 T-Cell-Specific Systemic and Mucosal Immunity against Herpes Simplex Virus with CpG-Peptide Complexes

Malgorzata Gierynska,1,2 Uday Kumaraguru,1 Seong-Kug Eo,3 Sujin Lee,1 Arthur Krieg,4 and Barry T. Rouse1*

Department of Microbiology, University of Tennessee, Knoxville, Tennessee 37996-0845,1 Department of Preclinical Sciences, Faculty of Veterinary Medicine, Warsaw Agricultural University, Warsaw, Poland;,2 Department of Microbiology, College of Veterinary Medicine, Chonbuk National University, Chonbuk, South Korea;,3 Coley Pharmaceutical Group, Wellesley, Massachusetts 024814

Received 22 January 2002/ Accepted 24 March 2002

Oligodeoxynucleotides (ODN) containing unmethylated CpG motifs exert powerful adjuvant activity in vivo and in vitro. Administered with antigen they induce a population of antigen-specific CD8+ T cells. In this study we immunized C57BL/6 mice with bioactive CpG ODN combined with an immunodominant epitope derived from herpes simplex virus (HSV) glycoprotein B (amino acids 498 to 505; SSIEFARL) and analyzed the magnitude and durability of the peptide-specific response. The effectiveness of the CD8+ T-cell response as measured by peptide-specific tetramers, peptide-induced intracellular gamma interferon expression, and resistance to systemic and mucosal challenge during the acute and memory phases was compared with the response induced by immunization with recombinant vaccinia virus encoding SSIEFARL as a minigene (VvgB498-505). Confirming the reports of others, our results demonstrate that the CpG ODN-peptide approach generates an antigen-specific CD8+ T-cell population, but the frequency of CD8+ T cells is lower than that induced by VvgB498-505. Nevertheless, the protection level was comparable when mice were systemically and mucosally challenged during the acute phase. However, such responses by both groups waned with time and were functionally less effective. Still, our results indicate that the CpG ODN-peptide immunization system holds promise as a means of selectively inducing a CD8+ T-cell response against HSV.

* Corresponding author. Mailing address: Department of Microbiology M-409, Walters Life Sciences Building, University of Tennessee, Knoxville, TN 37996-0845. Phone: (865) 974-4026. Fax: (865) 974-4007. E-mail: btr{at}utk.edu.

Journal of Virology, July 2002, p. 6568-6576, Vol. 76, No. 13
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.13.6568-6576.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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Copyright © 2002 by the American Society for Microbiology. All rights reserved.