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Infection and Immunity, October 2000, p. 5509-5516, Vol. 68, No. 10
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Adjuvant Activity of Monophosphoryl Lipid A for Nasal and Oral Immunization with Soluble or Liposome-Associated Antigen

Noel K. Childers,1,* Keri L. Miller,1 Giang Tong,1 Juan Carlos Llarena,1 Terrance Greenway,2 J. Terry Ulrich,3 and Suzanne M. Michalek2

Department of Pediatric Dentistry, School of Dentistry,1 and Department of Microbiology,2 University of Alabama at Birmingham, Birmingham, Alabama 35294-0007, and Corixa Corporation, Hamilton, Montana3

Received 3 April 2000/Returned for modification 4 May 2000/Accepted 30 June 2000

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 µg 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.

* Corresponding author. Mailing address: Department of Pediatric Dentistry, School of Dentistry, Room 308, University of Alabama at Birmingham, Birmingham, AL 35294-0007. Phone: (205) 934-3230. Fax: (205) 975-5737. E-mail: nkc{at}uab.edu.

Infection and Immunity, October 2000, p. 5509-5516, Vol. 68, No. 10
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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