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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

Authors :
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
Novartis Vaccines
Source :
Vaccine, Vaccine, 2019, 37 (2), pp.314-324. ⟨10.1016/j.vaccine.2018.10.008⟩, Vaccine, Elsevier, 2019, 37 (2), pp.314-324. ⟨10.1016/j.vaccine.2018.10.008⟩
Publication Year :
2019
Publisher :
Elsevier BV, 2019.

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.

Details

ISSN :
0264410X
Volume :
37
Database :
OpenAIRE
Journal :
Vaccine
Accession number :
edsair.doi.dedup.....491dec8874f57a985f7d1b36347f7a45
Full Text :
https://doi.org/10.1016/j.vaccine.2018.10.008