RT Journal Article
SR Electronic
T1 Rationally designed oral vaccines can set an evolutionary trap for <em>Salmonella</em> Typhimurium
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 824821
DO 10.1101/824821
A1 Médéric Diard
A1 Erik Bakkeren
A1 Daniel Hoces
A1 Verena Lentsch
A1 Markus Arnoldini
A1 Flurina Böhi
A1 Kathrin Schumann-Moor
A1 Jozef Adamcik
A1 Luca Piccoli
A1 Antonio Lanzavecchia
A1 Beth M. Stadtmueller
A1 Nicholas Donohue
A1 Marjan W. van der Woude
A1 Alyson Hockenberry
A1 Patrick H. Viollier
A1 Laurent Falquet
A1 Daniel Wüthrich
A1 Ferdinando Bonfiglio
A1 Adrian Egli
A1 Giorgia Zandomeneghi
A1 Raffaele Mezzenga
A1 Otto Holst
A1 Beat H. Meier
A1 Wolf-Dietrich Hardt
A1 Emma Slack
YR 2019
UL http://biorxiv.org/content/early/2019/10/31/824821.abstract
AB 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.One sentence summary By tracking vaccine-driven Salmonella evolution in the intestine, it is possible to rationally design oligovalent oral vaccines that generate an evolutionary trap.