Broad protective vaccination against systemic Escherichia coli with autotransporter antigens.

TitleBroad protective vaccination against systemic Escherichia coli with autotransporter antigens.
Publication TypeJournal Article
Year of Publication2023
AuthorsXing, Y, Clark, JR, Chang, JD, Chirman, DM, Green, S, Zulk, JJ, Jelinski, J, Patras, KA, Maresso, AW
JournalPLoS Pathog
Date Published2023 Feb
KeywordsAnimals, Bacteremia, Escherichia coli, Escherichia coli Infections, Extraintestinal Pathogenic Escherichia coli, Humans, Immunoglobulin G, Mice, Type V Secretion Systems, Urinary Tract Infections, Vaccination, Vaccines, Synthetic, Virulence Factors

Extraintestinal pathogenic Escherichia coli (ExPEC) is the leading cause of adult life-threatening sepsis and urinary tract infections (UTI). The emergence and spread of multidrug-resistant (MDR) ExPEC strains result in a considerable amount of treatment failure and hospitalization costs, and contribute to the spread of drug resistance amongst the human microbiome. Thus, an effective vaccine against ExPEC would reduce morbidity and mortality and possibly decrease carriage in healthy or diseased populations. A comparative genomic analysis demonstrated a gene encoding an invasin-like protein, termed sinH, annotated as an autotransporter protein, shows high prevalence in various invasive ExPEC phylogroups, especially those associated with systemic bacteremia and UTI. Here, we evaluated the protective efficacy and immunogenicity of a recombinant SinH-based vaccine consisting of either domain-3 or domains-1,2, and 3 of the putative extracellular region of surface-localized SinH. Immunization of a murine host with SinH-based antigens elicited significant protection against various strains of the pandemic ExPEC sequence type 131 (ST131) as well as multiple sequence types in two distinct models of infection (colonization and bacteremia). SinH immunization also provided significant protection against ExPEC colonization in the bladder in an acute UTI model. Immunized cohorts produced significantly higher levels of vaccine-specific serum IgG and urinary IgG and IgA, findings consistent with mucosal protection. Collectively, these results demonstrate that autotransporter antigens such as SinH may constitute promising ExPEC phylogroup-specific and sequence-type effective vaccine targets that reduce E. coli colonization and virulence.

Alternate JournalPLoS Pathog
PubMed ID36800400
PubMed Central IDPMC9937491
Grant ListU19 AI157981 / AI / NIAID NIH HHS / United States
U19 AI144297 / AI / NIAID NIH HHS / United States