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Journal of Virology, June 2002, p. 5565-5580, Vol. 76, No. 11
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.11.5565-5580.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Expression of Human Immunodeficiency Virus Type 1 gp120 from Herpes Simplex Virus Type 1-Derived Amplicons Results in Potent, Specific, and Durable Cellular and Humoral Immune Responses

Peter K. Hocknell,1 Rebecca D. Wiley,1 Xiuqing Wang,1 Thomas G. Evans,2 William J. Bowers,3,4 Tomas Hanke,5 Howard J. Federoff,1,3,4 and Stephen Dewhurst1,6*

Departments of Microbiology and Immunology,1 Neurology,3 Center for Aging and Developmental Biology,4 Cancer Center, University of Rochester Medical Center, Rochester, New York 14642,6 Division of Infectious and Immunologic Diseases, University of California Davis, Davis, California 95616,2 Molecular Immunology Group, Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, United Kingdom5

Received 19 February 2002/ Accepted 1 March 2002

Herpes simplex virus type 1 (HSV-1) infects a wide range of cells, including dendritic cells. Consequently, HSV-1 vectors may be capable of eliciting strong immune responses to vectored antigens. To test this hypothesis, an HSV-1 amplicon plasmid encoding human immunodeficiency virus type 1 gp120 was constructed, and murine immune responses to helper virus-free amplicon preparations derived from this construct were evaluated. Initial studies revealed that a single intramuscular (i.m.) injection of 106 infectious units (i.u.) of HSV:gp120 amplicon particles (HSV:gp120) elicited Env-specific cellular and humoral immune responses. A potent, CD8+-T-cell-mediated response to an H-2Dd-restricted peptide from gp120 (RGPGRAFVTI) was measured by a gamma interferon ELISPOT and was confirmed by standard cytotoxic-T-lymphocyte assays. Immunoglobulin G enzyme-linked immunosorbent assay analysis showed the induction of a strong, Env-specific antibody response. An i.m. or an intradermal administration of HSV:gp120 at the tail base elicited a more potent cellular immune response than did an intraperitoneal (i.p.) inoculation, although an i.p. introduction generated a stronger humoral response. The immune response to HSV:gp120 was durable, with robust cellular and humoral responses persisting at 171 days after a single 106-i.u. inoculation. The immune response to HSV:gp120 was also found to be dose dependent: as few as 104 i.u. elicited a strong T-cell response. Finally, HSV:gp120 elicited significant Env-specific cellular immune responses even in animals that had been previously infected with wild-type HSV-1. Taken together, these data strongly support the use of helper-free HSV-1 amplicon particles as vaccine delivery vectors.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, University of Rochester Medical Center, 601 Elmwood Ave., Box 672, Rochester, NY 14642. Phone: (585) 275-3216. Fax: (585) 473-2361. E-mail: stephen_dewhurst{at}urmc.rochester.edu.

Journal of Virology, June 2002, p. 5565-5580, Vol. 76, No. 11
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.11.5565-5580.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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