Research in context
Evidence before this study
We did a literature review of the cause and epidemiology of urinary tract infections, current therapies, and vaccine candidates. We searched the MEDLINE databases with the terms “urinary tract infection”, “cystitis”, and “uropathogenic Escherichia coli” for articles published in English between Jan 1, 1980, and Jan 13, 2017 (the date of our final search). Search terms were subsequently combined with: “placebo-controlled clinical trial”, “aetiology”, “epidemiology”, “prevalence”, “pathogenesis”, “therapy”, or “vaccine”. Some papers cited in the screened publications were also included, as were guidelines on urological infections, additional articles on antibiotic resistance and uropathogenic E coli pathogenicity, and information from company websites, government agencies, and the ClinicalTrials.gov registry.
Although we identified two vaccine candidates (targeting E coli and Proteus mirabilis, respectively) undergoing testing in murine models, we identified no other vaccine candidates in clinical development (human testing) targeting uropathogenic E coli or urinary tract infections in general. Additionally, we did an epidemiological study of urinary tract infections in community and hospital settings throughout Switzerland to assess the prevalence of E coli associated with urinary tract infections and to identify the O-serogroups of the predominant strains (unpublished). Pathogens associated with more than 3000 urinary tract infections were characterised and more than 1800 E coli strains isolated from urine were collected to identify the main O-serogroups.
Added value of this study
Our study shows a strong safety profile and high immunogenicity with durable and functional immune responses for the parenteral, multivalent E coli O-antigen bioconjugate vaccine. Additionally, this first-in human trial shows moderate protective efficacy against urinary tract infections with bacterial loads of 105 colony-forming units per mL or more. Collectively these findings support an early proof of concept for the development of E coli bioconjugate vaccines.
Implications of all the available evidence
Increases in antibiotic-resistant bacteria causing pyelonephritis and urosepsis call for further development of preventive approaches. Our study suggests that there is the potential for further investigation of a parenteral bioconjugate vaccine for prevention of extraintestinal E coli infections.