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Rationally designed oral vaccines can set an evolutionary trap for Salmonella Typhimurium

Diard, Médéric and Bakkeren, Erik and Hoces, Daniel and Lentsch, Verena and Arnoldini, Markus and Böhi, Flurina and Schumann-Moor, Kathrin and Adamcik, Jozef and Piccoli, Luca and Lanzavecchia, Antonio and Stadtmueller, Beth M. and Donohue, Nicholas and van der Woude, Marjan W. and Hockenberry, Alyson and Viollier, Patrick H. and Falquet, Laurent and Wüthrich, Daniel and Bonfiglio, Ferdinando and Egli, Adrian and Zandomeneghi, Giorgia and Mezzenga, Raffaele and Holst, Otto and Meier, Beat H. and Hardt, Wolf-Dietrich and Slack, Emma. (2019) Rationally designed oral vaccines can set an evolutionary trap for Salmonella Typhimurium.

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Abstract

Secretory antibody responses (Immunoglobulin A, IgA) against repetitive bacterial surface glycans, such as O-antigens and capsules, can protect against intestinal pathogenic Enterobacteriaceae . However, efficacy of such immune responses has been limited by rapid glycan evolution and phase-variation. Here, we track IgA-driven O-antigen variation in Salmonella Typhimurium, and use this to assemble an oligovalent oral vaccine which sets an evolutionary trap. IgA targeting all fitness-neutral O-antigen escape variants of Salmonella Typhimurium rapidly selected for mutants with very short O-antigen: a phenotype known to display major fitness costs and virulence attenuation in naive hosts. Evolutionary trap vaccination therefore represents an alternative concept in vaccine design. This approach capitalizes on the inevitable and rapid evolution of bacteria in the gut, and can combine protection of the individual with elimination of virulent enteropathogen reservoirs.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Infection Biology > Pathogen Evolution (Diard)
UniBasel Contributors:Diard, Médéric
Item Type:Working Paper
Publisher:bioRxiv
Note:Publication type according to Uni Basel Research Database: Discussion paper / Internet publication
Language:English
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Last Modified:04 May 2020 07:08
Deposited On:30 Apr 2020 15:14

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