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Clinical and Vaccine Immunology, May 2009, p. 699-705, Vol. 16, No. 5
1071-412X/09/$08.00+0     doi:10.1128/CVI.00370-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Potent Adjuvant Activity of Cationic Liposome-DNA Complexes for Genital Herpes Vaccines{triangledown}

David I. Bernstein,1* Rhonda D. Cardin,1 Fernando J. Bravo,1 Jane E. Strasser,1 Nicholas Farley,1 Claudia Chalk,1 Marla Lay,2 and Jeff Fairman2

Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio,1 Juvaris BioTherapeutics, Inc., Burlingame, California2

Received 9 October 2008/ Returned for modification 15 December 2008/ Accepted 1 March 2009

Development of a herpes simplex virus (HSV) vaccine is a priority because these infections are common. It appears that potent adjuvants will be required to augment the immune response to subunit HSV vaccines. Therefore, we evaluated cationic liposome-DNA complexes (CLDC) as an adjuvant in a mouse model of genital herpes. Using a whole-virus vaccine (HVAC), we showed that the addition of CLDC improved antibody responses compared to vaccine alone. Most important, CLDC increased survival, reduced symptoms, and decreased vaginal virus replication compared to vaccine alone or vaccine administered with monophosphoryl lipid A (MPL) plus trehalose dicorynomycolate (TDM) following intravaginal challenge of mice. When CLDC was added to an HSV gD2 vaccine, it increased the amount of gamma interferon that was produced from splenocytes stimulated with gD2 compared to the amount produced with gD2 alone or with MPL-alum. The addition of CLDC to the gD2 vaccine also improved the outcome following vaginal HSV type 2 challenge compared to vaccine alone and was equivalent to vaccination with an MPL-alum adjuvant. CLDC appears to be a potent adjuvant for HSV vaccines and should be evaluated further.

* Corresponding author. Mailing address: Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave., ML 6014, Cincinnati, OH 45229. Phone: (513) 636-7625. Fax: (513) 636-7682. E-mail: David.Bernstein{at}cchmc.org

{triangledown} Published ahead of print on 11 March 2009.

Clinical and Vaccine Immunology, May 2009, p. 699-705, Vol. 16, No. 5
1071-412X/09/$08.00+0     doi:10.1128/CVI.00370-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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