Adjuvant activity of monophosphoryl lipid A for nasal and oral immunization with soluble or liposome-associated antigen

The effectiveness of monophosphoryl lipid A (MPL) as a mucosal adjuvant was investigated following oral or intranasal (i.n.) administration of an aque ous adjuvant formulation of MPL (MPL-AF) added to soluble antigen or liposo mal antigen or incorporated into liposomal antigen membranes. Groups of BAL B/c female mice were immunized with 50 to 100 mu g of free or liposomal Str eptococcus mutans crude glucosyltransferase (C-GTF) with or without MPL-AF added to the vaccine or incorporated into the liposomal membrane, Plasma, s aliva, vaginal wash, and fecal extract samples were collected biweekly foll owing immunization and assessed for antigen-specific antibody activity by e nzyme-linked immunosorbent assay (ELISA). Mice immunized by the i.n. route had higher levels of salivary, plasma, and vaginal immunoglobulin A (IgA) a nti-C-GTF responses and higher levels of plasma Ige anti-C-GTP than the ora lly immunized groups. A second administration of the vaccine 14 weeks after the initial immunization resulted in an anamnestic response to C-GTF resul ting in 10-and 100-fold increases in saliva and plasma IgA and plasma IgG, respectively tin the i.n. immunized groups). Mice receiving a second i.n. i mmunization with liposomal antigen and MPL-AF had higher salivary IgA anti- C-GTF responses than mice immunized with antigen plus MPL-AF or liposomal a ntigen (P < 0.05). Plasma IgG anti-C-GTF activity was highest in mice immun ized by the i.n. route with antigen formulations containing MPL-AF (P < 0.0 5). These results demonstrate the effectiveness of MPL-AF as an adjuvant fo r potentiating mucosal and systemic immune responses to liposomal C-GTF fol lowing i.n. immunization.