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Clinical and Vaccine Immunology, November 2008, p. 1638-1643, Vol. 15, No. 11
1071-412X/08/$08.00+0     doi:10.1128/CVI.00167-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Phase I Study of a Herpes Simplex Virus Type 2 (HSV-2) DNA Vaccine Administered to Healthy, HSV-2-Seronegative Adults by a Needle-Free Injection System ^,

Ashok Cattamanchi,¹ Christine M. Posavad,^2,4* Anna Wald,^1,2,3 Yaela Baine,^8, Jennifer Moses,^2, Terry J. Higgins,⁵ Richard Ginsberg,^8, Richard Ciccarelli,⁹ Lawrence Corey,^1,2,4 and David M. Koelle^1,2,4,6,7

Department of Medicine, University of Washington, Seattle, Washington,¹ Department of Laboratory Medicine, University of Washington, Seattle, Washington,² Department of Epidemiology, University of Washington, Seattle, Washington,³ Program in Infectious Diseases, Fred Hutchinson Cancer Research Center, Seattle, Washington,⁴ Wyeth Vaccines, Wyeth, Pearl River, New York,⁵ Department of Global Health Medicine, University of Washington, Seattle, Washington,⁶ Benaroya Research Institute, Seattle, Washington,⁷ Apollon, Malvern, Pennsylvania,⁸ Wyeth, Collegeville, Pennsylvania⁹

Received 12 May 2008/ Returned for modification 4 June 2008/ Accepted 3 September 2008

We conducted a double-blind, vehicle-controlled, dose escalation safety and immunogenicity trial of a candidate herpes simplex virus type 2 (HSV-2) surface glycoprotein D2 (gD2) DNA vaccine administered by use of a needle-free device. Sixty-two healthy adults were randomized using a 4:1 vaccine-to-placebo ratio. Half of the participants were HSV-1 seronegative, and all were HSV-2 seronegative. Vaccine doses included 100 µg, 300 µg, 1,000 µg or 3,000 µg of a plasmid expressing the gD2 protein. Subjects received vaccine at 0, 4, 8, and 24 weeks. Some subjects received an additional 1,000-µg boost at 52 weeks. We found that the vaccine was safe and well tolerated, with most adverse events being local site reactions. No dose-limiting toxicities were observed. gD2-specific cytotoxic T-lymphocyte and lymphoproliferation responses were detected 2 weeks after the third vaccine injection in one of four HSV-1-seronegative, HSV-2-seronegative participants who received 3,000 µg of vaccine. A DNA-based vaccination strategy against HSV-2 appears to be safe and may generate a vaccine-specific cellular immune response, but high vaccine doses are likely needed to elicit an immune response in most vaccinees.

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* Corresponding author. Mailing address: Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Room D3-100, Seattle, WA 98109. Phone: (206) 667-6802. Fax: (206) 667-4411. E-mail: posavad{at}u.washington.edu

Published ahead of print on 10 September 2008.

We dedicate this study to the memory of Richard Ginsberg, who provided intellectual camaraderie and constant medical guidance for the clinical conduct of the trial, and to the memory of Jennifer Moses, who performed the T-cell immunogenicity assays.

Present address: GlaxoSmithKline, King of Prussia, PA.

Deceased.

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Clinical and Vaccine Immunology, November 2008, p. 1638-1643, Vol. 15, No. 11
1071-412X/08/$08.00+0     doi:10.1128/CVI.00167-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.