Nasal immunization with a fusion protein consisting of the hemagglutinin A antigenic region and the maltose-binding protein elicits CD11c(+) CD8(+) dendritic cells for induced long-term protective immunity.
We assessed the efficacy of a fusion protein consisting of the 25-kDa antigenic region of Porphyromonas gingivalis hemagglutinin A and the Escherichia coli maltose-binding protein (25k-hagA-MBP) as a nasal vaccine for the prevention of oral infection with P. gingivalis. Nasal immunization with 25k-hagA-MBP induced high levels of 25k-hagA-specific serum IgG, serum IgA, and salivary IgA antibodies in a Toll-like receptor 4 (TLR4)-dependent manner. These antibody responses were maintained for at least 1 year after immunization. Analysis of cytokine responses showed that nasal administration of 25k-hagA-MBP induced antigen-specific CD4(+) T cells producing interleukin 4 (IL-4) and IL-5, but not gamma interferon (IFN-γ), in the spleen and cervical lymph nodes (CLNs). Furthermore, increased numbers of CD11c(+) CD8α(+), but not CD11c(+) CD11b(+) or CD11c(+) B220(+), dendritic cells with upregulated expression of CD80, CD86, CD40, and major histocompatibility complex class II (MHC II) molecules were noted in the spleen, CLNs, and nasopharynx-associated lymphoreticular tissues (NALT). Interestingly, when 25k-hagA-MBP or cholera toxin (CT) was given intranasally to enable examination of their presence in neuronal tissues, the amounts of 25k-hagA-MBP were significantly lower than those of CT. Importantly, mice given 25k-hagA-MBP nasally showed a significant reduction in alveolar bone loss caused by oral infection with P. gingivalis, even 1 year after the immunization. These results suggest that 25k-hagA-MBP administered nasally would be an effective and safe mucosal vaccine against P. gingivalis infection and may be an important tool for the prevention of chronic periodontitis in humans.
Department of Microbiology and Immunology, Nihon University School of Dentistry at Matsudo, 2-870-1 Sakaecho-Nishi, Matsudo, Chiba 271-8587, Japan.
Yuan
Y
Du
Tomomi
T
Hashizume
Tomoko
T
Kurita-Ochiai
Satoshi
S
Yuzawa
Yoshimitsu
Y
Abiko
Masafumi
M
Yamamoto
D000276:Adjuvants, Immunologic; D000281:Administration, Intranasal; D016301:Alveolar Bone Loss / Q000517:prevention & control; D000818:Animals; D000942:Antigens, Bacterial; D001426:Bacterial Proteins / Q000737:chemistry / Q000276:immunology*; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016866:Bacteroidaceae Infections / Q000517:prevention & control; D039521:CD11c Antigen / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology; D037102:Lectins / Q000737:chemistry / Q000276:immunology; D058619:Maltose-Binding Proteins / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D016966:Porphyromonas gingivalis / Q000276:immunology* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism
D000276:Adjuvants, Immunologic; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D039521:CD11c Antigen; D016827:CD8 Antigens; D037102:Lectins; D058619:Maltose-Binding Proteins; D011993:Recombinant Fusion Proteins; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; C114923:hemagglutinin A, Porphyromonas gingivalis