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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

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-2D^d-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.

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