| Autor: |
Diard, Médéric, Bakkeren, Erik, Hoces, Daniel, Lentsch, Verena, Arnoldini, Markus, Böhi, Flurina, Schumann-Moor, Kathrin, Adamcik, Jozef, Piccoli, Luca, Lanzavecchia, Antonio, Stadtmueller, Beth, Donohue, Nicholas, van der Woude, Marjan, Hockenberry, Alyson, Viollier, Patrick, Falquet, Laurent, Wüthrich, Daniel, Bonfiglio, Ferdinando, Loverdo, Claude, Egli, Adrian, Zandomeneghi, Giorgia, Mezzenga, Raffaele, Holst, Otto, Meier, Beat, Hardt, Wolf-Dietrich, Slack, Emma |
| Přispěvatelé: |
Laboratoire Jean Perrin (LJP), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| Předmět: |
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| Popis: |
Secretory antibody responses (Immunoglobulin A, IgA) against repetitive bacterial surface glycans, such as O-antigens, can protect against intestinal pathogenic bacteria. However, vaccines that rely predominantly on secretory IgA for protection against non-Typhoidal salmonellosis often fail. Here we demonstrate that a major contributor to this failure is rapid immune escape, due to strong selective pressure exerted by high-avidity intestinal IgA. Interestingly, we found that IgA-escape initially occurs via a predictable narrow spectrum of Salmonella O-antigen variants that are fitness-neutral in naïve hosts. This could be attributed both to phase-variation, and to loss-of-function mutations in O-antigen-modifying enzymes. Via a vaccination regimen that simultaneously induced IgA against all observed O-antigen variants, rapid bacterial evolution could be switched from a hindrance into an advantage. Here, IgA generated a selective pressure resulting in fixation of mutations causing loss of polymerized O-antigen. When transmitted into naive hosts, these short O-antigen variants display compromised fitness and virulence, i.e. IgA-mediated pressure generates an evolutionary trade-off. Rational induction of IgA specificities that set “evolutionary traps” could reduce virulent enteropathogen reservoirs, even when sterilizing immunity cannot be achieved. This may become a powerful tool in the management of increasingly drug-resistant enteropathogenic bacteria. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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