Nasal vaccination with the 40-kilodalton outer membrane protein of Porphyromonas gingivalis and a nontoxic chimeric enterotoxin adjuvant induces long-term protective immunity with reduced levels of immunoglobulin E antibodies.
In this study, we demonstrated that the 40-kDa outer membrane protein of Porphyromonas gingivalis (40-kDa OMP) nasally administered with a nontoxic chimeric adjuvant that combines the A subunit of mutant cholera toxin E112K with the pentameric B subunit of heat-labile enterotoxin from enterotoxigenic Escherichia coli (mCTA/LTB) elicited a long-term protective immune response. Immunization with the 40-kDa OMP and mCTA/LTB induced high levels of 40-kDa-OMP-specific immunoglobulin G (IgG) and IgA antibodies (Abs) in sera and elicited a significant IgA anti-40-kDa OMP Ab response in saliva. These Ab responses were maintained for at least 1 year after the immunization. Although using adjuvant mCTA/LTB gave Ab responses in the saliva comparable to those obtained using native cholera toxin (nCT) as the adjuvant, the levels of total IgE and 40-kDa-OMP-specific IgE Abs as well as interleukin-4 levels induced by the immunization with mCTA/LTB were lower than those induced by the immunization with nCT. Importantly, IgG Abs generated by nasal immunization with the 40-kDa OMP plus mCTA/LTB inhibited the coaggregation and hemagglutinin activities of P. gingivalis. Furthermore, the mice given nasal 40-kDa OMP plus mCTA/LTB showed a significant reduction of alveolar bone loss caused by oral infection with P. gingivalis even 1 year after the immunization compared to the loss in unimmunized mice. Because mCTA/LTB is nontoxic, nasally administered 40-kDa OMP together with mCTA/LTB should be an effective and safe mucosal vaccine against P. gingivalis infection in humans and may be an important tool for the prevention of chronic periodontitis.
Momoi
Fumiki
F
Department of Microbiology and Immunology, Nihon University School of Dentistry at Matsudo, 2-870-1 Sakaecho-Nishi, Matsudo, Chiba 271-8587, Japan.
Hashizume
Tomomi
T
Kurita-Ochiai
Tomoko
T
Yuki
Yoshikazu
Y
Kiyono
Hiroshi
H
Yamamoto
Masafumi
M
D000276:Adjuvants, Immunologic; D000281:Administration, Intranasal; D016301:Alveolar Bone Loss / Q000382:microbiology / Q000517:prevention & control; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016866:Bacteroidaceae Infections / Q000517:prevention & control; D004768:Enterotoxins / Q000276:immunology*; D005260:Female; D018928:Immunity, Mucosal; D007073:Immunoglobulin E / Q000097:blood*; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D010518:Periodontitis / Q000150:complications / Q000382:microbiology / Q000517:prevention & control; D016966:Porphyromonas gingivalis / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology
D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D004768:Enterotoxins; D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins; D007073:Immunoglobulin E