A randomized phase 1/2a trial of ExPEC10V vaccine in adults with a history of UTI.
Journal
NPJ vaccines
ISSN: 2059-0105
Titre abrégé: NPJ Vaccines
Pays: England
ID NLM: 101699863
Informations de publication
Date de publication:
14 Jun 2024
14 Jun 2024
Historique:
received:
23
10
2023
accepted:
07
05
2024
medline:
15
6
2024
pubmed:
15
6
2024
entrez:
14
6
2024
Statut:
epublish
Résumé
The safety, reactogenicity, and immunogenicity of 3 doses of ExPEC10V (VAC52416), a vaccine candidate to prevent invasive Escherichia coli disease, were assessed in a phase 1/2a study (NCT03819049). In Cohort 1, ExPEC10V was well tolerated; the high dose was selected as optimal and further characterized in Cohort 2. Cohort 2 comprised a maximum 28-day screening, vaccination (Day 1), double-blind 181-day follow-up, and open-label long-term follow-up until Year 1. Healthy participants (≥60 years) with a history of urinary tract infection (UTI) within 5 years were randomized to receive ExPEC10V or placebo. The primary endpoint evaluated the safety and reactogenicity of ExPEC10V (solicited local and systemic AEs [until Day 15]; unsolicited AEs [until Day 30], SAEs [until Day 181], and immunogenicity [Day 30]) via multiplex electrochemiluminescent (ECL) and multiplex opsonophagocytic assay (MOPA). 416 participants (ExPEC10V, n = 278; placebo, n = 138) were included (mean age [SD], 68.8 [6.52] years; female, 79.6%; White, 96.1%). The incidence of solicited AEs was higher with ExPEC10V (local, 50.0% [n = 139]; systemic, 50.0% [n = 139]) than placebo (15.9% [n = 22]; 38.4% [n = 53]); rates of unsolicited AEs were comparable (ExPEC10V, 28.4% [n = 79]; placebo, 26.1% [n = 36]). No vaccine-related SAEs or deaths were reported. ExPEC10V elicited a robust antibody-mediated immunogenic response across all serotypes with ECL (Day 30 geometric mean fold increase, 2.33-8.18) and demonstrated functional opsonophagocytic killing activity across all measured serotypes (Day 30 geometric mean fold increase, 1.81-9.68). ExPEC10V exhibited an acceptable safety profile and a robust vaccine-induced functional immunogenic response in participants with a history of UTI. Clinical trial registration details: https://clinicaltrials.gov/study/NCT03819049 .
Identifiants
pubmed: 38877036
doi: 10.1038/s41541-024-00885-1
pii: 10.1038/s41541-024-00885-1
doi:
Banques de données
ClinicalTrials.gov
['NCT03819049']
Types de publication
Journal Article
Langues
eng
Pagination
106Informations de copyright
© 2024. The Author(s).
Références
Geurtsen, J. et al. Genomics and pathotypes of the many faces of Escherichia coli. FEMS Microbiol. Rev. https://doi.org/10.1093/femsre/fuac031 (2022).
Russo, T. A. & Johnson, J. R. Medical and economic impact of extraintestinal infections due to Escherichia coli: focus on an increasingly important endemic problem. Microbes Infect. 5, 449–456 (2003).
doi: 10.1016/S1286-4579(03)00049-2
pubmed: 12738001
Poolman, J. T. & Wacker, M. Extraintestinal pathogenic Escherichia coli, a common human pathogen: challenges for vaccine development and progress in the field. J. Infect. Dis. 213, 6–13 (2016).
doi: 10.1093/infdis/jiv429
pubmed: 26333944
Bonten, M. et al. Epidemiology of Escherichia coli bacteremia: a systematic literature review. Clin. Infect. Dis. 72, 1211–1219 (2021).
doi: 10.1093/cid/ciaa210
pubmed: 32406495
Doua, J. et al. Epidemiology, clinical features, and antimicrobial resistance of invasive Escherichia coli disease in patients admitted in tertiary care hospitals. Open Forum Infect. Dis. 10, ofad026 (2023).
doi: 10.1093/ofid/ofad026
pubmed: 36817744
pmcid: 9933942
Antimicrobial Resistance Collaborators. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet 399, 629–655 (2022).
doi: 10.1016/S0140-6736(21)02724-0
Poolman, J. T. & Anderson, A. S. Escherichia coli and Staphylococcus aureus: leading bacterial pathogens of healthcare associated infections and bacteremia in older-age populations. Expert Rev. Vaccines 17, 607–618 (2018).
doi: 10.1080/14760584.2018.1488590
pubmed: 29902092
Vihta, K. D. et al. Trends over time in Escherichia coli bloodstream infections, urinary tract infections, and antibiotic susceptibilities in Oxfordshire, UK, 1998-2016: a study of electronic health records. Lancet Infect. Dis. 18, 1138–1149 (2018).
doi: 10.1016/S1473-3099(18)30353-0
pubmed: 30126643
pmcid: 7612540
Raeispour, M. & Ranjbar, R. Antibiotic resistance, virulence factors and genotyping of uropathogenic Escherichia coli strains. Antimicrob. Resist. Infect. Control 7, 118 (2018).
doi: 10.1186/s13756-018-0411-4
pubmed: 30305891
pmcid: 6171155
Pitout, J. D. & DeVinney, R. Escherichia coli ST131: a multidrug-resistant clone primed for global domination. F1000Res https://doi.org/10.12688/f1000research.10609.1 (2017).
Miajlovic, H., Mac Aogain, M., Collins, C. J., Rogers, T. R. & Smith, S. G. J. Characterization of Escherichia coli bloodstream isolates associated with mortality. J. Med. Microbiol. 65, 71–79 (2016).
doi: 10.1099/jmm.0.000200
pubmed: 26518234
van der Mee-Marquet, N. L. et al. Marked increase in incidence for bloodstream infections due to Escherichia coli, a side effect of previous antibiotic therapy in the elderly. Front. Microbiol. 6, 646 (2015).
pubmed: 26175721
pmcid: 4485226
Ling, W. et al. Population-based incidence and characteristics of adult Escherichia coli bloodstream infection in Queensland, Australia, from 2000 to 2019. Open Forum Infect. Dis. 10, ofad071 (2023).
doi: 10.1093/ofid/ofad071
pubmed: 36968960
pmcid: 10034595
Weiner-Lastinger, L. M. et al. Antimicrobial-resistant pathogens associated with adult healthcare-associated infections: summary of data reported to the National Healthcare Safety Network, 2015-2017. Infect. Control Hosp. Epidemiol. 41, 1–18 (2020).
doi: 10.1017/ice.2019.296
pubmed: 31767041
Weiner, L. M. et al. Antimicrobial-resistant pathogens associated with healthcare-associated infections: summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2011-2014. Infect. Control Hosp. Epidemiol. 37, 1288–1301 (2016).
doi: 10.1017/ice.2016.174
pubmed: 27573805
pmcid: 6857725
Naylor, N. R. et al. The health and cost burden of antibiotic resistant and susceptible Escherichia coli bacteraemia in the English hospital setting: a national retrospective cohort study. PLoS ONE 14, e0221944 (2019).
doi: 10.1371/journal.pone.0221944
pubmed: 31504046
pmcid: 6736296
Abernethy, J. K. et al. Thirty day all-cause mortality in patients with Escherichia coli bacteraemia in England. Clin. Microbiol. Infect. 21, 251 e251–251 e258 (2015).
doi: 10.1016/j.cmi.2015.01.001
Terlizzi, M. E., Gribaudo, G. & Maffei, M. E. Uropathogenic Escherichia coli (UPEC) infections: virulence factors, bladder responses, antibiotic, and non-antibiotic antimicrobial strategies. Front. Microbiol. 8, 1566 (2017).
doi: 10.3389/fmicb.2017.01566
pubmed: 28861072
pmcid: 5559502
Pitout, J. D. Extraintestinal pathogenic Escherichia coli: a combination of virulence with antibiotic resistance. Front. Microbiol. 3, 9 (2012).
doi: 10.3389/fmicb.2012.00009
pubmed: 22294983
pmcid: 3261549
Medina, M. & Castillo-Pino, E. An introduction to the epidemiology and burden of urinary tract infections. Ther. Adv. Urol. 11, 1756287219832172 (2019).
doi: 10.1177/1756287219832172
pubmed: 31105774
pmcid: 6502976
Bou-Antoun, S. et al. Descriptive epidemiology of Escherichia coli bacteraemia in England, April 2012 to March 2014. Euro Surveill. https://doi.org/10.2807/1560-7917.ES.2016.21.35.30329 (2016).
Daga, A. P. et al. Escherichia coli bloodstream infections in patients at a university hospital: virulence factors and clinical characteristics. Front. Cell. Infect. Microbiol. 9, 191 (2019).
doi: 10.3389/fcimb.2019.00191
pubmed: 31245301
pmcid: 6563721
Weerdenburg, E. et al. Global distribution of O serotypes and antibiotic resistance in extraintestinal pathogenic Escherichia coli collected from the blood of patients with bacteremia across multiple surveillance studies. Clin. Infect. Dis. 76, e1236–e1243 (2023).
doi: 10.1093/cid/ciac421
pubmed: 35684979
Fierro, C. A. et al. Safety, reactogenicity, immunogenicity, and dose selection of 10-valent extraintestinal pathogenic Escherichia coli bioconjugate vaccine (VAC52416) in adults aged 60-85 years in a randomized, multicenter, interventional, first-in-human, phase 1/2a study. Open Forum Infect. Dis. 10, ofad417 (2023).
doi: 10.1093/ofid/ofad417
pubmed: 37608916
pmcid: 10442062
Frenck, R. W. Jr. et al. Safety and immunogenicity of a vaccine for extra-intestinal pathogenic Escherichia coli (ESTELLA): a phase 2 randomised controlled trial. Lancet Infect. Dis. 19, 631–640 (2019).
doi: 10.1016/S1473-3099(18)30803-X
pubmed: 31079947
Huttner, A. et al. Safety, immunogenicity, and preliminary clinical efficacy of a vaccine against extraintestinal pathogenic Escherichia coli in women with a history of recurrent urinary tract infection: a randomised, single-blind, placebo-controlled phase 1b trial. Lancet Infect. Dis. 17, 528–537 (2017).
doi: 10.1016/S1473-3099(17)30108-1
pubmed: 28238601
Matsumoto, T. et al. Distribution of extraintestinal pathogenic Escherichia coli O-serotypes and antibiotic resistance in blood isolates collected from patients in a surveillance study in Japan. J. Infect. Chemother. 28, 1445–1451 (2022).
doi: 10.1016/j.jiac.2022.07.001
pubmed: 35843539
Cryz, S. J. Jr., Cross, A. S., Sadoff, J. C. & Furer, E. Synthesis and characterization of Escherichia coli O18 O-polysaccharide conjugate vaccines. Infect. Immun. 58, 373–377 (1990).
doi: 10.1128/iai.58.2.373-377.1990
pubmed: 2105272
pmcid: 258465
Ciesielczuk, H. et al. Trends in ExPEC serogroups in the UK and their significance. Eur. J. Clin. Microbiol. Infect. Dis. 35, 1661–1666 (2016).
doi: 10.1007/s10096-016-2707-8
pubmed: 27329302
pmcid: 5035653
Lipworth, S. et al. Ten years of population-level genomic Escherichia coli and Klebsiella pneumoniae serotype surveillance informs vaccine development for invasive infections. Clin. Infect. Dis. 73, 2276–2282 (2021).
doi: 10.1093/cid/ciab006
pubmed: 33411882
pmcid: 8677521
Inoue, M. et al. Safety, tolerability and immunogenicity of the ExPEC4V (JNJ-63871860) vaccine for prevention of invasive extraintestinal pathogenic Escherichia coli disease: a phase 1, randomized, double-blind, placebo-controlled study in healthy Japanese participants. Hum. Vaccin. Immunother. 14, 2150–2157 (2018).
doi: 10.1080/21645515.2018.1474316
pubmed: 29771596
pmcid: 6183137
van Deursen, A. M. M. et al. Immunogenicity of the 13-Valent Pneumococcal Conjugate Vaccine in Older Adults With and Without Comorbidities in the Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA). Clin. Infect. Dis. 65, 787–795 (2017).
doi: 10.1093/cid/cix419
pubmed: 29017280
Patterson, S. et al. A post hoc assessment of duration of protection in CAPiTA (Community Acquired Pneumonia immunization Trial in Adults). Trials Vaccinol. 5, 92–96 (2016).
doi: 10.1016/j.trivac.2016.04.004
Juergens, C. et al. Late onset of injection site reactions after vaccination with the 13-valent pneumococcal conjugate vaccine in adult study populations. Hum. Vaccines & Immunother. 14, 1948–1956 (2018).
doi: 10.1080/21645515.2018.1452576
Moriel, D. G. et al. A novel protective vaccine antigen from the core Escherichia coli genome. mSphere https://doi.org/10.1128/mSphere.00326-16 (2016).
Taxt, A. M. et al. Characterization of immunological cross-reactivity between enterotoxigenic Escherichia coli heat-stable toxin and human guanylin and uroguanylin. Infect. Immun. 82, 2913–2922 (2014).
doi: 10.1128/IAI.01749-14
pubmed: 24778111
pmcid: 4097616