Enhanced type I immune response to a hepatitis B DNA vaccine by formulation with calcium- or aluminum phosphate.
DNA vaccines induce protective humoral and cell-mediated immune responses in several animal models. When compared with conventional vaccines, however, DNA vaccines often induce lower antibody titers. We have now found that formulation of a DNA vaccine encoding hepatitis B surface antigen with calcium- or aluminum phosphate adjuvants can increase antibody titers by 10-100-fold and decrease the immunogenic dose of DNA by 10-fold. Furthermore, boosting an HBs protein-primed response with the adjuvanted DNA vaccine resulted in a dramatic increase in the HBs-specific IgG2a response reflecting a shift towards a TH1 response. The mechanism by which aluminum phosphate exerts its adjuvant effect is not through increased expression of HBsAg in vivo; rather, the adjuvant appears to increase the number and affinity of HBs peptide antigen-specific IFN-gamma and IL-2 secreting T cells.
Wang
S
S
Department of Virus & Cell Biology, Merck Research Labs, West Point, PA 19486, USA.
Liu
X
X
Fisher
K
K
Smith
J G
JG
Chen
F
F
Tobery
T W
TW
Ulmer
J B
JB
Evans
R K
RK
Caulfield
M J
MJ
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D017607:Aluminum Compounds / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000818:Animals; D002130:Calcium Phosphates / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D004306:Dose-Response Relationship, Immunologic; D006510:Hepatitis B Antibodies / Q000096:biosynthesis; D006514:Hepatitis B Surface Antigens / Q000235:genetics / Q000276:immunology; D017325:Hepatitis B Vaccines / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007117:Immunization, Secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D010710:Phosphates / Q000494:pharmacology*; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*
D000276:Adjuvants, Immunologic; D017607:Aluminum Compounds; D002130:Calcium Phosphates; D016207:Cytokines; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D010710:Phosphates; D019444:Vaccines, DNA; C485828:alpha-tricalcium phosphate; C485830:tetracalcium phosphate; C485838:calcium phosphate, monobasic, anhydrous; C020243:calcium phosphate; C012714:aluminum phosphate; C485829:calcium phosphate, dibasic, anhydrous