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 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.
Childers
N K
NK
Department of Pediatric Dentistry, School of Dentistry, University of Alabama at Birmingham, Birmingham, Alabama 35294-0007, USA. nkc@uab.edu
Miller
K L
KL
Tong
G
G
Llarena
J C
JC
Greenway
T
T
Ulrich
J T
JT
Michalek
S M
SM
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000281:Administration, Intranasal; D000284:Administration, Oral; D000818:Animals; D000907:Antibodies, Bacterial / Q000032:analysis / Q000096:biosynthesis* / Q000097:blood; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000276:immunology*; D005260:Female; D005964:Glucosyltransferases / Q000276:immunology / Q000378:metabolism; D018928:Immunity, Mucosal; D007114:Immunization; D007070:Immunoglobulin A / Q000032:analysis / Q000097:blood; D007071:Immunoglobulin A, Secretory / Q000032:analysis; D007074:Immunoglobulin G / Q000097:blood; D008050:Lipid A / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000276:immunology; D008081:Liposomes / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D012463:Saliva / Q000276:immunology; D012995:Solubility; D013295:Streptococcus mutans / Q000201:enzymology / Q000276:immunology; D014621:Vagina / Q000276:immunology
D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D007070:Immunoglobulin A; D007071:Immunoglobulin A, Secretory; D007074:Immunoglobulin G; D008050:Lipid A; D008081:Liposomes; D005964:Glucosyltransferases; C048436:monophosphoryl lipid A