Enhancement of DNA vaccine potency using conventional aluminum adjuvants.
The immunogenicity and protective efficacy of DNA vaccines have been amply demonstrated in numerous animal models of infectious disease. However, the feasibility of DNA vaccines for human use is not yet known. In order to investigate potential means of increasing the potency of DNA vaccines, conventional adjuvants such as aluminum salts were tested. Coadministration of these adjuvants with DNA vaccines substantially enhanced the ability of these vaccines to induce antibody responses up to 100-fold in mice and guinea pigs, and 5-10-fold in non-human primates. Effective formulations had no demonstrable effect on the levels of antigen expression in situ and consisted of adjuvants that did not form complexes with the plasmid DNA; rather they exerted their effects on antigen after expression in situ. Therefore, the potency of DNA vaccines both in laboratory rodents and in non-human primates can be substantially increased by simple formulation with conventional aluminum adjuvants.
Ulmer
J B
JB
Department of Virus & Cell Biology, Merck Research Laboratories, West Point, PA, USA.
DeWitt
C M
CM
Chastain
M
M
Friedman
A
A
Donnelly
J J
JJ
McClements
W L
WL
Caulfield
M J
MJ
Bohannon
K E
KE
Volkin
D B
DB
Evans
R K
RK
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D017607:Aluminum Compounds / Q000494:pharmacology*; D000536:Aluminum Hydroxide / Q000494:pharmacology; D000818:Animals; D005260:Female; D006168:Guinea Pigs; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D002679:Pan troglodytes; D010710:Phosphates / Q000494:pharmacology; D019444:Vaccines, DNA / Q000276:immunology*
D000276:Adjuvants, Immunologic; D017607:Aluminum Compounds; D010710:Phosphates; D019444:Vaccines, DNA; D000536:Aluminum Hydroxide; C069096:aluminum hydroxyphosphate; C012714:aluminum phosphate