Rapid immunity to vaccination with woodchuck hepatitis virus surface antigen using cationic liposome-DNA complexes as adjuvant.
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.
Cote
Paul J
PJ
Department of Microbiology and Immunology, Georgetown University Medical Center, Washington, District of Columbia, USA.
Butler
Scott D
SD
George
Andrea L
AL
Fairman
Jeffery
J
Gerin
John L
JL
Tennant
Bud C
BC
Menne
Stephan
S
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000534:Alum Compounds / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D000954:Antigens, Surface / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004247:DNA / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006510:Hepatitis B Antibodies / Q000097:blood; D017325:Hepatitis B Vaccines / Q000276:immunology*; D017919:Hepatitis B Virus, Woodchuck / Q000276:immunology*; D007117:Immunization, Secondary / Q000379:methods; D007273:Injections, Intramuscular; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000096:biosynthesis; D008081:Liposomes / Q000008:administration & dosage / Q000494:pharmacology*; D008392:Marmota; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000954:Antigens, Surface; D006510:Hepatitis B Antibodies; D017325:Hepatitis B Vaccines; D008081:Liposomes; D014409:Tumor Necrosis Factor-alpha; C041524:aluminum sulfate; D007371:Interferon-gamma; D004247:DNA