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A highly immunogenic vaccine platform against encapsulated pathogens using chimeric probiotic Escherichia coli membrane vesicles
Department of Bacteriology I, National Institute of Infectious Diseases, 1-23-1, Toyama, Shinjuku-ku, Tokyo, Japan.
Department of Pathology, National Institute of Infectious Diseases, 1-23-1, Toyama, Shinjuku-ku, Tokyo, Japan.
Department of Bacteriology I, National Institute of Infectious Diseases, 1-23-1, Toyama, Shinjuku-ku, Tokyo, Japan; Department of Pediatric Dentistry/Special Needs Dentistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, Japan.
College of Science and Engineering, Kanto Gakuin University, 1-50-1, Mutsuura-higashi, Kanazawa-ku, Kanagawa, Yokohama, Japan.
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2022 (English)In: npj Vaccines, E-ISSN 2059-0105, Vol. 7, no 1, article id 153Article in journal (Refereed) Published
Abstract [en]

Vaccines against infectious diseases should elicit potent and long-lasting immunity, ideally even in those with age-related decline in immune response. Here we report a rational polysaccharide vaccine platform using probiotic Escherichia coli-derived membrane vesicles (MVs). First, we constructed a probiotic E. coli clone harboring the genetic locus responsible for biogenesis of serotype 14 pneumococcal capsular polysaccharides (CPS14) as a model antigen. CPS14 was found to be polymerized and mainly localized on the outer membrane of the E. coli cells. The glycine-induced MVs displayed the exogenous CPS14 at high density on the outermost surface, on which the CPS14 moiety was covalently tethered to a lipid A-core oligosaccharide anchor. In in vivo immunization experiments, CPS14+MVs, but not a mixture of free CPS14 and empty MVs, strongly elicited IgG class-switch recombination with a Th1/Th2-balanced IgG subclass distribution without any adjuvant. In addition, CPS14+MVs were structurally stable with heat treatment and immunization with the heat-treated MVs-elicited CPS14-specific antibody responses in mouse serum to levels comparable to those of non-treated CPS14+MVs. Notably, the immunogenicity of CPS14+MVs was significantly stronger than those of two currently licensed vaccines against pneumococci. The CPS14+MV-elicited humoral immune responses persisted for 1 year in both blood and lung. Furthermore, the CPS14+MV vaccine was widely efficacious in mice of different ages. Even in aged mice, vaccination resulted in robust production of CPS14-specific IgG that bound to the pneumococcal cell surface. Taken together, the present probiotic E. coli MVs-based vaccine platform offers a promising, generalizable solution against encapsulated pathogens.

Place, publisher, year, edition, pages
Nature Publishing Group, 2022. Vol. 7, no 1, article id 153
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Immunology in the medical area
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URN: urn:nbn:se:umu:diva-201460DOI: 10.1038/s41541-022-00572-zISI: 000888807700001Scopus ID: 2-s2.0-85142614736OAI: oai:DiVA.org:umu-201460DiVA, id: diva2:1716720
Available from: 2022-12-06 Created: 2022-12-06 Last updated: 2025-08-28Bibliographically approved

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Ramstedt, Madeleine

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