Assessment of outer membrane vesicles of periodontopathic bacterium Porphyromonas gingivalis as possible mucosal immunogen.
Periodontitis is the most prevalent infectious disease and related to oral and systemic health, therefore novel prophylaxis to prevent the disease is highly desirable. Here, we assessed the outer membrane vesicles (OMVs) of a keystone periodontal pathogen, Porphyromonas gingivalis, as a candidate mucosal immunogen and adjuvant for a periodontitis vaccine. The structural and functional stability of OMVs, demonstrated by proteinase K resistance and ability to withstand long-term storage, are considered advantageous for carrying the OMV components into the host immune system. Intranasal vaccination of OMVs in mice elicited production of P. gingivalis-specific antibodies in blood and saliva by OMVs in a dose-dependent manner, which was dramatically enhanced by addition of a TLR3 agonist, Poly(I:C). Serum samples from mice immunized with OMVs plus Poly(I:C) adjuvant [OMV+Poly(I:C)] showed significant inhibition of gingipain proteolytic activity of not only the vaccine strain, but also heterologous strains. The viability of P. gingivalis was also decreased by preincubation with OMV+Poly(I:C)-immunized sera, while the killing effect was partially blocked by heat-inactivation of the sera. Saliva samples from mice immunized with OMV+Poly(I:C) enhanced bacterial agglutination of both the vaccine and heterologous strains. In an oral infection mouse model, the numbers of P. gingivalis in the oral cavity were significantly decreased in mice intranasally immunized with OMV+Poly(I:C) as compared to mock (only Poly[I:C])-immunized mice. The high levels of serum IgG (including IgG1 and IgG2a) and salivary S-IgA were elicited in mice intranasally immunized with OMV+Poly(I:C), which were maintained for at least 28 and 18weeks, respectively, after immunization. An experiment examining the accumulation of OMVs after intranasal immunization in proximal organs and an intracerebral injection experiment confirmed the safety of OMVs. Based on our results, we propose that intranasal immunization with OMV+Poly(I:C) is a feasible vaccine strategy in the context of bacterial clearance and safety.
['Nakao|Ryoma|R|', 'Hasegawa|Hideki|H|', 'Dongying|Bai|B|', 'Ohnishi|Makoto|M|', 'Senpuku|Hidenobu|H|']
D000276:Adjuvants, Immunologic D000281:Administration, Intranasal D000818:Animals D000907:Antibodies, Bacterial D001428:Bacterial Vaccines D055252:Cell-Derived Microparticles D005260:Female D018928:Immunity, Mucosal D007074:Immunoglobulin G D051379:Mice D008807:Mice, Inbred BALB C D009092:Mucous Membrane D010518:Periodontitis D011070:Poly I-C D011119:Polynucleotides D016966:Porphyromonas gingivalis D012463:Saliva
Outer membrane vesicles Porphyromonas gingivalis Poly(I:C) Intranasal immunization Periodontal disease