Antigen levels and antibody titers after DNA vaccination.
DNA vaccination generates strong cellular and humoral immunity in animal models. The mechanisms by which plasmid DNA uptake and expression after intramuscular injection lead to immune responses are not well understood. In particular, the importance of antigen expression levels on subsequent antibody immune responses has not been established. We found that a chemiluminescent assay for alkaline phosphatase allows measurement of antigen levels of secreted alkaline phosphatase (SEAP) in vivo after intramuscular injection of a wide range of plasmid doses. The mice produced antibodies to the alkaline phosphatase reporter gene and both antigen levels and antibody titers were measured over time. We found that the correlation between initial antigen level and antibody response was high (r = 0.74, p < 0.001) and remained high even after accounting for the dose of plasmid injected (r = 0.61, p < 0.001). The correlation between DNA dose and antibody titer was statistically significant (r = 0.53, p < 0.001) but was reduced to almost zero after we accounted for initial antigen levels.
Chastain
M
M
Department of Virus and Cell Biology, Merck Research Laboratories, Sumneytown Pike, WP26-145, West Point, PA 19486, USA. mike_chastain@merck.com
Simon
A J
AJ
Soper
K A
KA
Holder
D J
DJ
Montgomery
D L
DL
Sagar
S L
SL
Casimiro
D R
DR
Middaugh
C R
CR
D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D000906:Antibodies / Q000097:blood*; D000917:Antibody Formation; D000941:Antigens / Q000097:blood*; D004306:Dose-Response Relationship, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015870:Gene Expression; D051379:Mice; D008807:Mice, Inbred BALB C; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*
D000906:Antibodies; D000941:Antigens; D019444:Vaccines, DNA; D000469:Alkaline Phosphatase