Potent protective cellular immune responses generated by a DNA vaccine encoding HSV-2 ICP27 and the E. coli heat labile enterotoxin.
A mouse model was employed to evaluate protective cellular immune responses induced by an immediate early antigen of HSV-2. Particle-mediated DNA vaccination of mice with a DNA plasmid-encoding ICP27 resulted in the induction of ICP27-specific IFN-gamma and TNF-alpha production in Balb/c mice, but little protection to intranasal challenge with wild type HSV-2. However, when the DNA vaccine was supplemented with as little as 50ng of a vector encoding the A and B subunits of the Escherichia coli heat labile enterotoxin (LT), animals were profoundly protected from morbidity and mortality. The ICP27+LT-mediated protection was correlated with a large increase in ICP27-specific IFN-gamma and TNF-alpha production but cytokine-specific monoclonal antibody treatment at the time of challenge showed that protection was mediated predominantly by IFN-gamma. Furthermore, depletion of T cell subsets prior to infectious challenge demonstrated that removal of either CD8+ or CD4+ T cells impaired protection with CD8+ T cells appearing to play a direct effector role. These data demonstrate that augmented cellular immune responses resulting from LT vector plus antigen vector administration to the skin are biologically significant, leading to enhanced protection against mucosal pathogenic challenge.
Haynes
Joel R
JR
PowderJect Vaccines Inc., Middleton, WI, USA. joel.haynes@ligocyte.com
Arrington
Joshua
J
Dong
Lichun
L
Braun
Ralph P
RP
Payne
Lendon G
LG
D000595:Amino Acid Sequence; D000818:Animals; D001427:Bacterial Toxins / Q000235:genetics / Q000276:immunology*; D016827:CD8 Antigens / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D004768:Enterotoxins / Q000235:genetics / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D029968:Escherichia coli Proteins / Q000235:genetics / Q000276:immunology*; D006561:Herpes Simplex / Q000276:immunology* / Q000517:prevention & control*; D018258:Herpesvirus 2, Human / Q000235:genetics / Q000276:immunology*; D022283:Herpesvirus Vaccines / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*
D001427:Bacterial Toxins; D016827:CD8 Antigens; D016207:Cytokines; D004768:Enterotoxins; D000939:Epitopes; D029968:Escherichia coli Proteins; D022283:Herpesvirus Vaccines; D019444:Vaccines, DNA; D014764:Viral Proteins; C027538:heat-labile enterotoxin, E coli