A bivalent outer membrane vesicle-based intranasal vaccine to prevent infection of periodontopathic bacteria |
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| Institution: | 1. Department of Bacteriology I, National Institute of Infectious Diseases, Tokyo 162-8640, Japan;2. Division of Microbiology and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8514, Japan;3. Department of Microbiology and Immunology, School of Dentistry at Matsudo, Nihon University, Chiba 271-8587, Japan;4. Department of Influenza Virus Research Center, National Institute of Infectious Diseases, Tokyo 208-0011, Japan;5. Department of Pathology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan;2. Division of Academic Affairs, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand;3. Regional Health Promotion Center 5, Na Mueang, Mueang Ratchaburi, Ratchaburi 70000, Thailand;4. The Academy of Science, The Royal Society of Thailand, Dusit, Bangkok 10300, Thailand;1. Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku, Tokyo 162-8640, Japan;2. Laboratory of Precision Immunology, Center for Intractable Diseases and ImmunoGenomics, National Institutes of Biomedical Innovation, Health and Nutrition, 7-6-8, Saito-Asagi, Ibaraki City, Osaka 567-0085, Japan;3. Department of Life Science and Medical Bioscience, Waseda University, 2-2 Wakamatsucho Shinjuku, Tokyo 162-8480, Japan;4. Sumitomo Pharma. Co., Ltd., 3-1-98, Kasugade-naka, Konohana-ku, Osaka 554-0022, Japan;5. Research Center for Influenza and Respiratory Viruses, National Institute of Infectious Diseases, Gakuen 4-7-1, Musashimurayama-shi, Tokyo 208-0011, Japan;6. Laboratory of Aging and Immune Regulation, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871, Japan;7. Department of Virology and Immunology, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan;1. Vaccine and Infectious Disease Organization (VIDO), University of Saskatchewan, 120 Veterinary Road, Saskatoon, Saskatchewan S7N5E3, Canada;2. Toxicology Graduate Program, University of Saskatchewan, 44 Campus Drive, Saskatoon, Saskatchewan S7N 5B3, Canada;3. Department of Veterinary Microbiology Sciences, Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Drive, Saskatoon, Saskatchewan S7N 5B4, Canada;4. Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Drive, Saskatoon, Saskatchewan S7N 5B4, Canada;5. School of Public Health, Vaccinology and Immunotherapeutics, University of Saskatchewan, 52 Campus Drive, Saskatoon, Saskatchewan, Canada;1. State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China;2. Community Health Management Service Center, Longgang District People’s Hospital of Shenzhen, Shenzhen, China;3. Department of Infection Control, Longgang District People’s Hospital of Shenzhen, Shenzhen, China |
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| Abstract: | Periodontal disease has become a serious public health problem, not only causing tooth loss, but also inducing chronic disorders of extra-oral organs. The present study assessed an intranasal vaccine strategy to prevent periodontal disease using outer membrane vesicles (OMVs) of two major periodontopathic bacteria, Porphyromonas gingivalis (Pg) and Aggregatibacter actinomycetemcomitans (Aa). We compared the morphology, composition, and immune activity between OMVs of Pg strain ATCC 33277 and Aa strain Y4. Aa OMVs had a smoother surface and stronger lipid A activity compared to Pg OMVs. The in vitro immune activity elicited by Aa OMVs in macrophage-like cells was remarkably stronger than that of Pg OMVs. Intranasal immunization of mice with Aa OMVs alone resulted in robust, humoral immune responses in blood and saliva. Despites the intrinsically low mucosal immunogenicity of Pg OMVs alone, using Aa OMVs as a mucosal adjuvant strongly enhanced Pg-specific immune responses, resulting in both serum IgG and salivary IgA, both of which aggregated Pg and Aa cells. Furthermore, Aa OMVs were found to be a more potent mucosal adjuvant than Poly(I:C) in the context of enhancing the production of Pg-specific IgG (especially IgG2a) and IgA. In addition, in a randomized, blinded study, mice oral challenged with Pg and Aa after intranasal immunization with Pg OMVs and Aa OMVs had significantly decreased numbers of both microorganisms compared to mock-immunized mice. Furthermore, in an intracerebral injection mouse model, there were no serious adverse effects on the brain even after administrating a dose of OMVs as same as that used for intranasal administration. Taken together, the bivalent OMV intranasal vaccine may be effective in preventing colonization of periodontopathic bacteria in the oral cavity and related systemic disorders associated with periodontal diseases. |
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| Keywords: | Outer membrane vesicles (OMVs) Vaccines Periodontal disease |
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