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Infect Immun ; 68(10): 5509-16, 2000 Oct.
Article in English | MEDLINE | ID: mdl-10992447

ABSTRACT

The effectiveness of monophosphoryl lipid A (MPL) as a mucosal adjuvant was investigated following oral or intranasal (i.n.) administration of an aqueous adjuvant formulation of MPL (MPL-AF) added to soluble antigen or liposomal antigen or incorporated into liposomal antigen membranes. Groups of BALB/c female mice were immunized with 50 to 100 microg of free or liposomal Streptococcus mutans crude glucosyltransferase (C-GTF) with or without MPL-AF added to the vaccine or incorporated into the liposomal membrane. Plasma, saliva, vaginal wash, and fecal extract samples were collected biweekly following immunization and assessed for antigen-specific antibody activity by enzyme-linked immunosorbent assay (ELISA). Mice immunized by the i.n. route had higher levels of salivary, plasma, and vaginal immunoglobulin A (IgA) anti-C-GTF responses and higher levels of plasma IgG anti-C-GTF than the orally immunized groups. A second administration of the vaccine 14 weeks after the initial immunization resulted in an anamnestic response to C-GTF resulting in 10- and 100-fold increases in saliva and plasma IgA and plasma IgG, respectively (in the i.n. immunized groups). Mice receiving a second i.n. immunization with liposomal antigen and MPL-AF had higher salivary IgA anti-C-GTF responses than mice immunized with antigen plus MPL-AF or liposomal antigen (P < 0.05). Plasma IgG anti-C-GTF activity was highest in mice immunized by the i.n. route with antigen formulations containing MPL-AF (P < 0.05). These results demonstrate the effectiveness of MPL-AF as an adjuvant for potentiating mucosal and systemic immune responses to liposomal C-GTF following i.n. immunization.


Subject(s)
Adjuvants, Immunologic/administration & dosage , Antibodies, Bacterial/biosynthesis , Antigens, Bacterial/immunology , Immunization , Lipid A/analogs & derivatives , Liposomes/immunology , Administration, Intranasal , Administration, Oral , Animals , Antibodies, Bacterial/analysis , Antibodies, Bacterial/blood , Antigens, Bacterial/administration & dosage , Female , Glucosyltransferases/immunology , Glucosyltransferases/metabolism , Immunity, Mucosal , Immunoglobulin A/analysis , Immunoglobulin A/blood , Immunoglobulin A, Secretory/analysis , Immunoglobulin G/blood , Lipid A/administration & dosage , Lipid A/immunology , Mice , Mice, Inbred BALB C , Saliva/immunology , Solubility , Streptococcus mutans/enzymology , Streptococcus mutans/immunology , Vagina/immunology
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