V. Tedeschi et al., A SPECIFIC ANTIBODY-RESPONSE TO HCV E2 ELICITED IN MICE BY INTRAMUSCULAR INOCULATION OF PLASMID DNA CONTAINING CODING SEQUENCES FOR E2, Hepatology, 25(2), 1997, pp. 459-462
As the chimpanzee, the only reliable animal model for hepatitis C viru
s (HCV) infection, is impractical for early stage testing of HCV vacci
ne candidates, we have evaluated the immune response in mice to an exp
erimental plasmid based HCV vaccine, We used this system because DNA v
accines can be rapidly constructed without the necessity of large scal
e protein production and purification, In this preliminary study we te
sted the immune response in mice to HCV envelope glycoprotein, E2, ind
uced by a eukaryotic expression plasmid, Protein expression was monito
red by immunofluorescence in transfected tissue culture cells, Each mo
use was inoculated intramuscular with 100 mu g plasmid DNA and some mi
ce were boosted after 5 weeks, Among 12 BALB/C mice inoculated, 10 dev
eloped antibody to E2 by the second week, The antibody levels increase
d steadily before reaching a plateau in mice receiving the booster, bu
t in the nonboosted mice the antibody declined over time, The serum fr
om one mouse was tested against a series of overlapping peptides cover
ing most of E2. This serum contained antibodies recognizing two distin
ct epitopes beginning at amino acid 57 and amino acid 113 but no antib
ody was directed against peptides representing the hypervariable regio
n of E2, antibody to which is thought to be important in HCV neutraliz
ation, We have shown that the use of plasmid based vaccines can induce
a specific immune response in mice against HCV antigens, This system
should be useful as the first step in vaccine development.