RRC ID 59280
Author Mitobe J, Sinha R, Mitra S, Nag D, Saito N, Shimuta K, Koizumi N, Koley H.
Title An attenuated Shigella mutant lacking the RNA-binding protein Hfq provides cross-protection against Shigella strains of broad serotype.
Journal PLoS Negl Trop Dis
Abstract Few live attenuated vaccines protect against multiple serotypes of bacterial pathogen because host serotype-specific immune responses are limited to the serotype present in the vaccine strain. Here, immunization with a mutant of Shigella flexneri 2a protected guinea pigs against subsequent infection by S. dysenteriae type 1 and S. sonnei strains. This deletion mutant lacked the RNA-binding protein Hfq leading to increased expression of the type III secretion system via loss of regulation, resulting in attenuation of cell viability through repression of stress response sigma factors. Such increased antigen production and simultaneous attenuation were expected to elicit protective immunity against Shigella strains of heterologous serotypes. Thus, the vaccine potential of this mutant was tested in two guinea pig models of shigellosis. Animals vaccinated in the left eye showed fewer symptoms upon subsequent challenge via the right eye, and even survived subsequent intestinal challenge. In addition, oral vaccination effectively induced production of immunoglobulins without severe side effects, again protecting all animals against subsequent intestinal challenge with S. dysenteriae type 1 or S. sonnei strains. Antibodies against common virulence proteins and the O-antigen of S. flexneri 2a were detected by immunofluorescence microscopy. Reaction of antibodies with various strains, including enteroinvasive Escherichia coli, suggested that common virulence proteins induced protective immunity against a range of serotypes. Therefore, vaccination is expected to cover not only the most prevalent serotypes of S. sonnei and S. flexneri 2a, but also various Shigella strains, including S. dysenteriae type 1, which produces Shiga toxin.
Volume 11(7)
Pages e0005728
Published 2017-7
DOI 10.1371/journal.pntd.0005728
PII PNTD-D-16-02058
PMID 28727722
PMC PMC5544247
MeSH Animals Cross Protection* Disease Models, Animal Dysentery, Bacillary / immunology Dysentery, Bacillary / pathology Dysentery, Bacillary / prevention & control* Gene Deletion* Guinea Pigs Host Factor 1 Protein / deficiency* Male Microbial Viability Serogroup Shigella / genetics* Shigella / immunology* Shigella Vaccines / administration & dosage Shigella Vaccines / genetics Shigella Vaccines / immunology* Survival Analysis Vaccines, Attenuated / administration & dosage Vaccines, Attenuated / genetics Vaccines, Attenuated / immunology Virulence
IF 4.487
Times Cited 5
Resource
Pathogenic bacteria Shigella flexneri 2b GTC01922 Shigella flexneri 3a GTC01924 Shigella flexneri 6 GTC01927