Specific antibodies induced by nasally administered 40-kDa outer membrane protein of Porphyromonas gingivalis inhibits coaggregation activity of P. gingivalis

Namikoshi, Jun; Otake, Shigeo; Maeba, Satomi; Hayakawa, Mitsuo; Abiko, Yoshimitsu; Yamamoto, Masafumi

doi:10.1016/s0264-410x(03)00576-0

Cited by 47 publications

(39 citation statements)

References 42 publications

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“…In this regard, it has been shown that nasal immunization with the weak protein Ag OVA plus mCT elicited OVA-specific S-IgA Ab responses in the submandibular glands (SMGs) in addition to other mucosal effector lymphoid tissues (4,5). Others have shown that mice given the nasal 40-kDa outer membrane protein of Porphyromonas gingivalis and nCT as mucosal adjuvant displayed significant levels of outer membrane protein-specific plasma IgG and IgA, as well as mucosal S-IgA Ab responses in saliva and nasal secretions (6).…”

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confidence: 99%

Nasal Cholera Toxin Elicits IL-5 and IL-5 Receptor α-Chain Expressing B-1a B Cells for Innate Mucosal IgA Antibody Responses

Kataoka

Fujihashi

Sekine

et al. 2007

The Journal of Immunology

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In this study, we examine whether native cholera toxin (nCT) as a mucosal adjuvant can support trinitrophenyl (TNP)-LPS-specific mucosal immune responses. C57BL/6 mice were given nasal TNP-LPS in the presence or absence of nCT. Five days later, significantly higher levels of TNP-specific mucosal IgA Ab responses were induced in the nasal washes, saliva, and plasma of mice given nCT plus TNP-LPS than in those given TNP-LPS alone. High numbers of TNP-specific IgA Ab-forming cells were also detected in mucosal tissues such as the nasal passages (NPs), the submandibular glands (SMGs), and nasopharyngeal-associated lymphoreticular tissue of mice given nCT. Flow cytometric analysis showed that higher numbers of surface IgA+, CD5+ B cells (B-1a B cells) in SMGs and NPs of mice given nasal TNP-LPS plus nCT than in those given TNP-LPS alone. Furthermore, increased levels of IL-5R α-chain were expressed by B-1a B cells in SMGs and NPs of mice given nasal TNP-LPS plus nCT. Thus, CD4+ T cells from these mucosal effector lymphoid tissues produce high levels of IL-5 at both protein and mRNA levels. When mice were treated with anti-IL-5 mAb, significant reductions in TNP-specific mucosal IgA Ab responses were noted in external secretions. These findings show that nasal nCT as an adjuvant enhances mucosal immune responses to a T cell-independent Ag due to the cross-talk between IL-5Rα+ B-1a B cells and IL-5-producing CD4+ T cells in the mucosal effector lymphoid tissues.

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confidence: 99%

Nasal Cholera Toxin Elicits IL-5 and IL-5 Receptor α-Chain Expressing B-1a B Cells for Innate Mucosal IgA Antibody Responses

Kataoka

Fujihashi

Sekine

et al. 2007

The Journal of Immunology

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“…The findings of these studies together with our results in the present study indicate that mucosal adjuvants such as mCTA/LTB are required for the induction of the protective immune responses against oral infection with P. gingivalis when the 40-kDa OMP is given by mucosal routes. CT and LT have been used widely as adjuvants for mucosal immunization, and our results indicate that the nasal administration of nCT with the 40-kDa OMP has an adjuvant effect and induces 40-kDa-OMP-specific mucosal IgA, as well as IgG and IgA Abs in serum (43). However, despite these beneficial attributes, CT and LT are unsuitable for use in humans because they cause severe diarrhea (51).…”

Section: Fig 3 Total Ige Ab Levels (A) 40-kda-omp-specific Ige Ab mentioning

confidence: 95%

“…IgA Abs were not detected in either serum or saliva samples. Indeed, the 40-kDa OMP without an adjuvant is a weak immunogen when given via the nasal route (43). Our previous studies have demonstrated that transcutaneous administration of the 40-kDa OMP without an adjuvant elicits a substantial IgG but not IgA Ab response in the sera and saliva of mice (36) and rats (30).…”

Section: Fig 3 Total Ige Ab Levels (A) 40-kda-omp-specific Ige Ab mentioning

confidence: 99%

“…Indeed, one of our previous studies demonstrated that the nasal administration of the 40-kDa OMP plus CT elicits 40-kDa-OMP-specific secretory immunoglobulin A (IgA) Abs in the saliva, as well as IgG Abs in serum, that inhibit the coaggregation activity of P. gingivalis (43). However, though the combination of the 40-kDa OMP with the adjuvant CT was shown to be effective, CT and LT cause severe diarrhea and thus are unsuitable for use in humans.…”

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confidence: 99%

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Nasal Vaccination with the 40-Kilodalton Outer Membrane Protein ofPorphyromonas gingivalisand a Nontoxic Chimeric Enterotoxin Adjuvant Induces Long-Term Protective Immunity with Reduced Levels of Immunoglobulin E Antibodies

et al. 2008

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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.Chronic periodontitis is a common oral inflammatory disease that causes the breakdown of periodontal tissue, including the resorption of alveolar bone, and as a consequence, tooth loss (8). Furthermore, recent studies have suggested that chronic periodontitis influences systemic conditions such as cardiovascular diseases, diabetes, and osteoporosis (5,10,19,28,39,41,45). Hence, the prevention of periodontitis is important for both oral and systemic health.Porphyromonas gingivalis, a gram-negative anaerobic bacterium, has been shown previously to be one of the major pathogens in chronic periodontitis. The colonization of gingival tissues by this bacterium is considered to be the first step in the pathogenic process of periodontal disease resulting in tissue destruction (24, 37). Molecules such as fimbriae, hemagglutinins, aggregation factors, and lipopolysaccharides responsible for colonization have been identified previously as virulence factors (24,37). An outer membrane protein having a molecular mass of 40 kDa produced by P. gingivalis (40-kDa OMP) is a key virulence factor involved in the coaggregation activity of P. gingivalis (23). Furthermore, this OMP has been shown previously to be a hemin-binding protein (49). The 40-kDa OMP resides both on the cell surface and in extracellular vesicles and is found on many strains of P. gingivalis (1,22,23,47).Previous studies have demonstrated that ...

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“…For example, the 40-kDa outer membrane protein of P. gingivalis (40k-OMP) is a key virulence factor for coaggregation (9) and hemagglutination (10), and is conserved among many strains (11). Previous studies have shown that IgG Abs induced by the nasal administration of recombinant (r) 40k-OMP with an adjuvant inhibited coaggregation by P. gingivalis (12). Furthermore, either oral, nasal or sublingual immunization with r40k-OMP prevented alveolar bone loss in response to a P. gingivalis challenge (13,14,15).…”

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confidence: 99%

Comparison of Mucosal Immune Response after Oral, Nasal or Sublingual Immunization with an Outer Membrane Protein of Porphyromonas Gingivalis

2014

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Mucosal immunization would provide an easy and safe measure in preventing infectious diseases by facilitating mass immunization. In order to represent a promising strategy for mucosal vaccination, oral, nasal, or sublingual immunizations of mice with a recombinant 40-kDa outer membrane protein of Porphyromonas gingivalis (r40k-OMP) and cholera toxin (CT) as a mucosal adjuvant were performed, and mucosal and systemic immune responses were compared. Administration of the antigen via the mucosal routes, such as orally, nasally or sublingually, equally elicited significant levels of r40k-OMP-specific IgG in the serum and high numbers of r40k-OMP-specific antibody-forming cells (AFCs) in the spleen. Nasal and sublingual immunization of mice also induced high levels of mucosal IgA antibodies (Abs) in the saliva and nasal washes compared to oral immunization.Subsequently, these immunizations confirmed the Ab titers by revealing significant numbers of r40k-OMP-specific AFCs in the submandibular glands, nasopharyngealassociated lymphoreticular tissue, and nasal passages. In contrast, mice that were orally immunized with r40k-OMP plus CT exhibited significantly increased antibody secreting cells in Peyerʼs patches and intestinal lamina propria, although lower level of cells were detected in nasal or sublingual immunization. These results have suggested that both nasal and sublingual immunization are more effective for prevention of periodontal disease compared to oral immunization.

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Specific antibodies induced by nasally administered 40-kDa outer membrane protein of Porphyromonas gingivalis inhibits coaggregation activity of P. gingivalis

Cited by 47 publications

References 42 publications

Nasal Cholera Toxin Elicits IL-5 and IL-5 Receptor α-Chain Expressing B-1a B Cells for Innate Mucosal IgA Antibody Responses

Nasal Cholera Toxin Elicits IL-5 and IL-5 Receptor α-Chain Expressing B-1a B Cells for Innate Mucosal IgA Antibody Responses

Nasal Vaccination with the 40-Kilodalton Outer Membrane Protein ofPorphyromonas gingivalisand a Nontoxic Chimeric Enterotoxin Adjuvant Induces Long-Term Protective Immunity with Reduced Levels of Immunoglobulin E Antibodies

Comparison of Mucosal Immune Response after Oral, Nasal or Sublingual Immunization with an Outer Membrane Protein of Porphyromonas Gingivalis

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