Immunization Against Hepatitis B Virus by Mucosal Administration of Antigen–Antibody Complexes

Antigen–antibody complexes have been shown to enhance immune responses against several antigens given by parenteral immunization. Herein, we have evaluated the potential of administering such immunostimulatory complexes by a mucosal route. Hepatitis B surface antigen (HBsAg) complexed with antibodies against HBsAg (anti-HBs) (HBsAg/Ab) was administered to BALB/c mice by intranasal inhalation. HBsAg by itself did not induce immune responses, whereas with HBsAg/Ab complexes, both systemic and mucosal immune responses were observed and these could be modulated by adjuvants. With HBsAg/Ab (1 or 10 μg), anti-HBs antibodies induced were predominantly of the IgG₁ isotype (Th2-like). In contrast, anti-HBs induced by HBsAg/Ab plus cholera toxin (CT) or oligodeoxynucleotides (ODN) containing immunostimulatory CpG motifs (CpG) (1 μg each) were predominantly IgG_2a (Th1-like). Results from this study indicate that HBsAg/Ab complexes can induce strong humoral immune repsonses when delivered by a noninvasive route, whether used alone or in combination with other mucosal adjuvants.