Potent adjuvant activity of cationic liposome-DNA complexes for genital herpes vaccines.
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.
Bernstein
David I
DI
Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio 45229, USA. David.Bernstein@cchmc.org
Cardin
Rhonda D
RD
Bravo
Fernando J
FJ
Strasser
Jane E
JE
Farley
Nicholas
N
Chalk
Claudia
C
Lay
Marla
M
Fairman
Jeff
J
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D002478:Cells, Cultured; D004247:DNA / Q000494:pharmacology*; D005260:Female; D006558:Herpes Genitalis / Q000517:prevention & control*; D022301:Herpes Simplex Virus Vaccines / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008081:Liposomes / Q000494:pharmacology*; D046911:Macromolecular Substances / Q000494:pharmacology*; D051379:Mice; D013154:Spleen / Q000276:immunology; D016019:Survival Analysis; D014621:Vagina / Q000821:virology; D014779:Virus Replication / Q000276:immunology
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D022301:Herpes Simplex Virus Vaccines; D008081:Liposomes; D046911:Macromolecular Substances; D007371:Interferon-gamma; D004247:DNA