1. Mixed mucosal-parenteral immunizations with the broadly conserved pathogenic Escherichia coli antigen SslE induce a robust mucosal and systemic immunity without affecting the murine intestinal microbiota
- Author
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Mariagrazia Pizza, Mickaël Desvaux, Grégory Jubelin, Juliette Vinot, Barbara Baudner, Ugo D'Oro, Annick Bernalier-Donadille, Cecilia Buonsanti, Ilham Naili, Microbiologie Environnement Digestif Santé (MEDIS), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), GlaxoSmithKline [Siena, Italy] (GSK), Marie Sklodowska-Curie Actions ITN EID DISCo FP7-PEOPLE-607611, Universite Clermont-Auvergne and Universita degli studi Roma Tre, INRA Clermont-Ferrand-Theix-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), GlaxoSmithKline, Glaxo Smith Kline, Novartis Vaccines, Siena, Italy, and Novartis Vaccines
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Virulence Factors ,[SDV]Life Sciences [q-bio] ,030231 tropical medicine ,Immunization, Secondary ,Pathogenic E. coli ,Gut microbiota ,Biology ,Gut flora ,Injections, Intramuscular ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Antigen ,Pathogenic Escherichia coli ,Immunity ,Sepsis ,Escherichia coli ,Animals ,030212 general & internal medicine ,SsLe ,Immunity, Mucosal ,Administration, Intranasal ,Escherichia coli Infections ,ComputingMilieux_MISCELLANEOUS ,Mice, Inbred BALB C ,Intramuscular ,General Veterinary ,General Immunology and Microbiology ,Escherichia coli Vaccines ,Escherichia coli Proteins ,Reverse vaccinology ,Public Health, Environmental and Occupational Health ,biology.organism_classification ,Antibodies, Bacterial ,Gastrointestinal Microbiome ,3. Good health ,Vaccination ,Infectious Diseases ,Intranasal ,Immunization ,Immunology ,Cytokines ,Molecular Medicine ,[SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology - Abstract
International audience; Emergence and dissemination of multidrug resistance among pathogenic Escherichia coli have posed a serious threat to public health across developing and developed countries. In combination with a flexible repertoire of virulence mechanisms, E. coli can cause a vast range of intestinal (InPEC) and extraintestinal (ExPEC) diseases but only a very limited number of antibiotics still remains effective against this pathogen. Hence, a broad spectrum E. coli vaccine could be a promising alternative to prevent the burden of such diseases, while offering the potential for covering against several InPEC and ExPEC at once. SslE, the Secreted and Surface-associated Lipoprotein of E. coli, is a widely distributed protein among InPEC and ExPEC. SslE functions ex vivo as a mucinase capable of degrading mucins and reaching the surface of mucus-producing epithelial cells. SslE was identified by reverse vaccinology as a protective vaccine candidate against an ExPEC murine model of sepsis, and further shown to be cross-effective against other ExPEC and InPEC models of infection. In this study, we aimed to gain insight into the immune response to antigen SslE and identify an immunization strategy suited to generate robust mucosal and systemic immune responses. We showed, by analyzing T cell and antibody responses, that mice immunized with SslE via an intranasal prime followed by two intramuscular boosts developed an enhanced overall immune response compared to either intranasal-only or intramuscular-only protocols. Importantly, we also report that this regimen of immunization did not impact the richness of the murine gut microbiota, and mice had a comparable cecal microbial composition, whether immunized with SslE or PBS. Collectively, our findings further support the use of SslE in future vaccination strategies to effectively target both InPEC and ExPEC while not perturbing the resident gut microbiota.
- Published
- 2019
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