Data Entry: Please note that the research database will be replaced by UNIverse by the end of October 2023. Please enter your data into the system https://universe-intern.unibas.ch. Thanks

Login for users with Unibas email account...

Login for registered users without Unibas email account...

 
A rationally designed oral vaccine induces immunoglobulin A in the murine gut that directs the evolution of attenuated Salmonella variants
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
 
ID 4631343
Author(s) Diard, Médéric; Bakkeren, Erik; Lentsch, Verena; Rocker, Andrea; Bekele, Nahimi Amare; Hoces, Daniel; Aslani, Selma; Arnoldini, Markus; Böhi, Flurina; Schumann-Moor, Kathrin; Adamcik, Jozef; Piccoli, Luca; Lanzavecchia, Antonio; Stadtmueller, Beth M.; Donohue, Nicholas; van der Woude, Marjan W.; Hockenberry, Alyson; Viollier, Patrick H.; Falquet, Laurent; Wüthrich, Daniel; Bonfiglio, Ferdinando; Loverdo, Claude; Egli, Adrian; Zandomeneghi, Giorgia; Mezzenga, Raffaele; Holst, Otto; Meier, Beat H.; Hardt, Wolf-Dietrich; Slack, Emma
Author(s) at UniBasel Diard, Médéric
Year 2021
Title A rationally designed oral vaccine induces immunoglobulin A in the murine gut that directs the evolution of attenuated Salmonella variants
Journal Nature Microbiology
Volume 6
Number 7
Pages / Article-Number 830-841
Mesh terms Administration, Oral; Animals; Antibodies, Bacterial, immunology; Antigenic Variation; Bacterial Proteins, genetics; Evolution, Molecular; Genetic Fitness; Hexosyltransferases, genetics; Immune Evasion; Immunity, Mucosal; Immunoglobulin A, immunology; Intestines, immunology, microbiology; Mice; Mutation; O Antigens, genetics, immunology; Salmonella Infections, microbiology, prevention & control; Salmonella Vaccines, administration & dosage, immunology; Salmonella typhimurium, genetics, immunology, pathogenicity; Vaccines, Attenuated, administration & dosage, immunology; Virulence
Abstract The ability of gut bacterial pathogens to escape immunity by antigenic variation-particularly via changes to surface-exposed antigens-is a major barrier to immune clearance; 1; . However, not all variants are equally fit in all environments; 2,3; . It should therefore be possible to exploit such immune escape mechanisms to direct an evolutionary trade-off. Here, we demonstrate this phenomenon using Salmonella enterica subspecies enterica serovar Typhimurium (S.Tm). A dominant surface antigen of S.Tm is its O-antigen: a long, repetitive glycan that can be rapidly varied by mutations in biosynthetic pathways or by phase variation; 4,5; . We quantified the selective advantage of O-antigen variants in the presence and absence of O-antigen-specific immunoglobulin A and identified a set of evolutionary trajectories allowing immune escape without an associated fitness cost in naive mice. Through the use of rationally designed oral vaccines, we induced immunoglobulin A responses blocking all of these trajectories. This selected for Salmonella mutants carrying deletions of the O-antigen polymerase gene wzyB. Due to their short O-antigen, these evolved mutants were more susceptible to environmental stressors (detergents or complement) and predation (bacteriophages) and were impaired in gut colonization and virulence in mice. Therefore, a rationally induced cocktail of intestinal antibodies can direct an evolutionary trade-off in S.Tm. This lays the foundations for the exploration of mucosal vaccines capable of setting evolutionary traps as a prophylactic strategy.
Publisher Nature Publishing Group
ISSN/ISBN 2058-5276
URL https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611113/
edoc-URL https://edoc.unibas.ch/85254/
Full Text on edoc No
Digital Object Identifier DOI 10.1038/s41564-021-00911-1
PubMed ID http://www.ncbi.nlm.nih.gov/pubmed/34045711
ISI-Number WOS:000655565300001
Document type (ISI) Journal Article
 
   

MCSS v5.8 PRO. 0.338 sec, queries - 0.000 sec ©Universität Basel  |  Impressum   |    
29/03/2024