Complexes of cationic
liposomes and non-coding
DNA (CLDC) have shown promise as
vaccine adjuvant. Using the woodchuck animal model of hepatitis B virus (HBV)
infection, the immunogenic effects of CLDC were evaluated following vaccination with three doses of woodchuck hepatitis virus
surface antigen (WHsAg) adjuvanted with either CLDC or conventional
alum and administered intramuscularly (im) or subcutaneously (sc). IM vaccination with WHsAg and CLDC elicited
antibodies earlier, in more woodchucks, and with higher titers than WHsAg and
alum. After two
vaccine doses, antibody titers were higher following im than sc administration. Woodchucks administered two
vaccine doses sc received the third
vaccine dose im, and antibody responses reached titers comparable to those elicited by im administration. Following the second
vaccine dose, im vaccination with WHsAg and CLDC induced T cell responses to WHsAg and selected WHs
peptides and expression of the leukocyte surface marker CD8 and of the Th1
cytokines interferon-gamma and
tumor necrosis factor alpha in woodchucks. T cell responses and CD8/
cytokine expression were diminished in woodchucks from the other groups suggesting that this
vaccine regimen induced a skew toward Th1 immune responses. The present study in woodchucks demonstrates that CLDC-adjuvanted WHsAg
vaccine administered im resulted in a more rapid induction of humoral and cellular immune responses compared to conventional,
alum-adjuvanted WHsAg
vaccine. While less rapid, the immune responses following sc administration can prime the im immune responses. This adjuvant activity of CLDC over
alum may be beneficial for therapeutic vaccination in chronic HBV
infection.