Safety and immunogenicity of an adjuvanted Escherichia coli adhesin vaccine in healthy women with and without histories of recurrent urinary tract infections: results from a first-in-human phase 1 study

References

• National Disease and Therapeutic Index, IMS Health, Plymouth Meeting, PA. 2014. ISC# 595.0, 595.9, 597.8, 599.0.
   Google Scholar
• Foxman B, Barlow R, D’Arcy H, Gillespie B, Sobel JD. Urinary tract infection: self-reported incidence and associated costs. Ann Epidemiol. 2000;10(8):509–15. doi:10.1016/s1047-2797(00)00072-7.
   PubMed Web of Science ®Google Scholar
• Foxman B. Epidemiology of urinary tract infections: incidence, morbidity, and economic costs. Dis Mon. 2003;49(2):53–70. doi:10.1067/mda.2003.7.
   PubMed Web of Science ®Google Scholar
• Urologist UTI Survey. Sequoia Sciences, Inc. and HRA Research; 2010
   Google Scholar
• van Duin D, Cober E, Richter SS, Perez F, Kalayjian RC, Salata RA, Evans S, Fowler VG, Kaye KS, Bonomo RA. Impact of therapy and strain type on outcomes in urinary tract infections caused by carbapenem-resistant Klebsiella pneumoniae. J Antimicrob Chemother. 2015 Apr;70(4):1203–11. doi:10.1093/jac/dku495.
   PubMed Web of Science ®Google Scholar
• Fingar K, Washington R. Trends in Hospital Readmissions for Four High-Volume Conditions, 2009-2013. Healthcare Cost and Utilization Project; 2015. Statistical Brief #196. p. 1–10.
   Google Scholar
• Johnston KJ, Thorpe KE, Jacob JT, Murphy DJ. The incremental cost of infections associated with multidrug-resistant organisms in the inpatient hospital setting-A national estimate. Health Serv Res. 2019;54(4):782–92. doi:10.1111/1475-6773.13135.
   PubMed Web of Science ®Google Scholar
• Sakellariou C, Gurntke S, Steinmetz I, Kohler C, Pfeifer Y, Gastmeier P, Schwab F, Kola A, Deja M, Leistner R. Sepsis Caused by Extended-Spectrum Beta-Lactamase (ESBL)-Positive K. pneumoniae and E. coli: comparison of Severity of Sepsis, Delay of Anti-Infective Therapy and ESBL Genotype. PLoS One. 2016;11(7):e0158039. doi:10.1371/journal.pone.0158039.
   PubMed Web of Science ®Google Scholar
• Levy MM, Gesten FC, Phillips GS, Terry KM, Seymour CW, Prescott HC, Friedrich M, Iwashyna TJ, Osborn T, Lemeshow S. Mortality Changes Associated with Mandated Public Reporting for Sepsis. The Results of the New York State Initiative. Am J Respir Crit Care Med. 2018;198(11):1406–12. doi:10.1164/rccm.201712-2545OC.
   PubMed Web of Science ®Google Scholar
• Hatfield KM, Dantes RB, Baggs J, Sapiano MRP, Fiore AE, Jernigan JA, Epstein L. Assessing Variability in Hospital-Level Mortality Among U.S. Medicare Beneficiaries with Hospitalizations for Severe Sepsis and Septic Shock. Crit Care Med. 2018;6(11):1753–60. doi:10.1097/CCM.0000000000003324.
   Google Scholar
• Critchley IA, Cotroneo N, Pucci MJ, Mendes R. The burden of antimicrobial resistance among urinary tract isolates of Escherichia coli in the United States in 2017. PLoS One. 2019;14(12):e0220265. doi:10.1371/journal.pone.0220265.
   PubMed Web of Science ®Google Scholar
• Jernigan JA, Hatfield KM, Wolford H, Nelson RE, Olubajo B, Reddy SC, McCarthy N, Paul P, McDonald LC, Kallen A, et al. Multidrug-Resistant Bacterial Infections in U.S. Hospitalized Patients, 2012-2017. N Engl J Med. 2020;382(14):1309–19. doi:10.1056/NEJMoa1914433.
   PubMed Web of Science ®Google Scholar
• Hayakawa K, Gattu S, Marchaim D, Bhargava A, Palla M, Alshabani K, Gudur UM, Pulluru H, Bathina P, Sundaragiri PR, et al. Epidemiology and risk factors for isolation of Escherichia coli producing CTX-M-type extended-spectrum beta-lactamase in a large U.S. Medical Center. Antimicrob Agents Chemother. 2013;57(8):4010–18. doi:10.1128/AAC.02516-12.
   PubMed Web of Science ®Google Scholar
• Marchaim D, Chopra T, Bhargava A, Bogan C, Dhar S, Hayakawa K, Pogue JM, Bheemreddy S, Blunden C, Shango M, et al. Recent exposure to antimicrobials and carbapenem-resistant Enterobacteriaceae: the role of antimicrobial stewardship. Infect Control Hosp Epidemiol. 2012;33(8):817–30. doi:10.1086/666642.
   PubMed Web of Science ®Google Scholar
• Hayden MK, Lin MY, Lolans K, Weiner S, Blom D, Moore NM, Fogg L, Henry D, Lyles R, Thurlow C, et al. Prevention of colonization and infection by Klebsiella pneumoniae carbapenemase-producing enterobacteriaceae in long-term acute-care hospitals. Clin Infect Dis. 2015;60(8):1153–61. doi:10.1093/cid/ciu1173.
   PubMed Web of Science ®Google Scholar
• Gupta K, Hooton TM, Roberts PL, Stamm WE. Patient-Initiated Treatment of Uncomplicated Recurrent Urinary Tract Infections in Young Women. Ann Intern Med. 2001;135:9–16. doi:10.7326/0003-4819-135-1-200107030-00004.
   PubMed Web of Science ®Google Scholar
• Gupta K, Hooton TM, Naber KG, Wullt B, Colgan R, Miller LG, Moran GJ, Nicolle LE, Raz R, Schaeffer AJ, et al. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis. 2011;52(5):e103–e120. doi:10.1093/cid/ciq257.
   PubMed Web of Science ®Google Scholar
• Hooton TM, Roberts PL, Cox ME, Stapleton AE. Voided Midstream Urine Culture and Acute Cystitis in Premenopausal Women. N Engl J Med. 2013;369:1883–91. doi:10.1056/NEJMoa1302186.
   PubMed Web of Science ®Google Scholar
• Abbo LM, Hooton TM. Antimicrobial Stewardship and Urinary Tract Infections. Antibiotics. 2014;3:174–92. doi:10.3390/antibiotics3020174.
   Google Scholar
• Hung CS, Bouckaert J, Hung D, Pinkner J, Widberg C, DeFusco A, Auguste CG, Strouse R, Langermann S, Waksman G, et al. Structural basis of tropism of Escherichia coli to the bladder during urinary tract infection. Mol Microbiol. 2002;44(4):903–15. doi:10.1046/j.1365-2958.2002.02915.x.
   PubMed Web of Science ®Google Scholar
• Martinez JJ, Mulvey MA, Schilling JD, Pinkner JS, Hultgren SJ. Type 1 pilus-mediated bacterial invasion of bladder epithelial cells. EMBO J. 2000;19:2803–12. doi:10.1093/emboj/19.12.2803.
   PubMed Web of Science ®Google Scholar
• Wright KJ, Seed PC, Hultgren SJ. Development of intracellular bacterial communities of uropathogenic Escherichia coli depends on type 1 pili. Cell Microbiol. 2007;9:2230–41. doi:10.1111/j.1462-5822.2007.00952.x.
   PubMed Web of Science ®Google Scholar
• Langermann S, Palaszynski S, Barnhart M, Auguste G, Pinkner JS, Burlein J. Prevention of mucosal Escherichia coli infection by FimH-adhesin-based systemic vaccination. Science. 1997;276:607–11. doi:10.1126/science.276.5312.607.
   PubMed Web of Science ®Google Scholar
• Langermann S, Mollby R, Burlein JE, Palaszynski SR, Auguste CG, DeFusco A, Strouse R, Schenerman M, Hultgren S, Pinkner J, et al. Vaccination with fimH adhesin protects cynomolgus monkeys from colonization and infection by uropathogenic Escherichia coli. J Infect Dis. 2000;181:774–78. doi:10.1086/315258.
   PubMed Web of Science ®Google Scholar
• Thankavel K, Madison B, Ikeda T, Malaviya R, Shah AH, Arumugam PM, Abraham SN. Localization of a domain in the FimH adhesin of Escherichia coli type 1 fimbriae capable of receptor recognition and use of a domain-specific antibody to confer protection against experimental urinary tract infection. J Clin Invest. 1997;100:1123–36. doi:10.1172/JCI119623.
   PubMed Web of Science ®Google Scholar
• Poggio TV, La Torre JL, Scodeller EA. Intranasal immunization with a recombinant truncated FimH adhesin adjuvanted with CpG oligodeoxynucleotides protects mice against uropathogenic Escherichia coli challenge. Can J Microbiol. 2006;52:1093–102. doi:10.1139/w06-065.
   PubMed Web of Science ®Google Scholar
• O’Brien VP, Hannan TJ, Yu L, Livny J, Roberson EDO, Schwartz DJ, Souza S, Mendelsohn CL, Colonna M, Lewis AL, et al. A mucosal imprint left by prior Escherichia coli bladder infection sensitizes to recurrent disease. Nature Microbiol. 2016;2:16196. doi:10.1038/nmicrobiol.2016.196.
   PubMed Web of Science ®Google Scholar
• Schwarz TF, Spaczynski M, Schneider A, Wysocki J, Galaj A, Perona P, Poncelet S, Zahaf T, Hardt K, Descamps D, et al. HPV Study Group for Adult Women. Immunogenicity and tolerability of an HPV-16/18 AS04-adjuvanted prophylactic cervical cancer vaccine in women aged 15-55 years. Vaccine. 2009;27:581–87. doi:10.1016/j.vaccine.2008.10.088.
   PubMed Web of Science ®Google Scholar
• Rubin RH, Shapiro ED, Andriole VT, Davis RJ, Stamm WE. Evaluation of New Anti-Infective Drugs for the Treatment of Urinary Tract Infection. Clin Infect Dis. 1992;15(Supplement 1):S216–S227. doi:10.1093/clind/15.Supplement_1.S216.
   PubMedGoogle Scholar
• Czaja CA, Stamm WE, Stapleton AE, Roberts PL, Hawn TR, Scholes D, Samadpour M, Hultgren SJ, Hooton TM. Prospective Cohort Study of Microbial and Inflammatory Events Immediately Preceding Escherichia coli Recurrent Urinary Tract Infection in Women. J Infect Dis. 2009;200(4):528–36. doi:10.1086/600385.
   PubMed Web of Science ®Google Scholar
• Hooton TM, Roberts PL, Stapleton AE. Cefpodoxime vs Ciprofloxacin for Short-Course Treatment of Acute Uncomplicated Cystitis: A Randomized Trial. JAMA. 2012;307(6):583–89. doi:10.1001/jama.2012.80.
   PubMed Web of Science ®Google Scholar
• Huttner A, Hatz C, van den Dobbelsteen G, Abbanat D, Hornacek A, Frölich R, Dreyer AM, Martin P, Davies T, Fae K, 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. 2017;17(5):528–37. doi:10.1016/S1473-3099(17)30108-1.
   PubMed Web of Science ®Google Scholar
• Starks CM, Miller MM, Broglie PM, Cubbison J, Martin SM, Eldridge GR. Optimization and qualification of an assay that demonstrates that a fimH vaccine induces functional antibody responses in women with histories of urinary tract infections. Hum Vaccin Immunother. 2020. in press. doi:10.1080/21645515.2020.1770034.
   PubMed Web of Science ®Google Scholar
• De Nisco NJ, Neugent M, Mull J, Chen L, Kuprasertkul A, de Souza Santos M, Palmer KL, Zimmern P, Orth K. Direct Detection of Tissue-Resident Bacteria and Chronic Inflammation in the Bladder Wall of Postmenopausal Women with Recurrent Urinary Tract Infection. J Mol Biol. 2019;431(21):4368–79. doi:10.1016/j.jmb.2019.04.008.
   PubMed Web of Science ®Google Scholar
• Schlager TA, LeGallo R, Innes D, Hendley JO, Peters CA. B Cell Infiltration and Lymphonodular Hyperplasia in Bladder Submucosa of Patients with Persistent Bacteriuria and Recurrent Urinary Tract Infections. J Urol. 2011;186:2359–64. doi:10.1016/j.juro.2011.07.114.
   PubMed Web of Science ®Google Scholar
• Janssen Research & Development LLC. A study of three different doses of VAC52416 (ExPEC10V) in adults aged 60 to 85 years in stable health. [accessed 2020 Jul 20]. Clinicaltrials.govAccessionNCT03819049Accession NCT03819049
   Google Scholar
• Nicolle LE, Bradley S, Colgan R, Rice JC, Schaeffer A, Hooton TM. IDSA Guidelines for Asymptomatic Bacteriuria. Clin Infect Dis. 2005;40:643–54. doi:10.1086/427507.
   PubMed Web of Science ®Google Scholar
• Wurpel DJ, Beatson SA, Totsika M, Petty NK, Schembri MA. Chaperone-usher Fimbriae of Escherichia coli. PLoS One. 2013;8(1):e52835. doi:10.1371/journal.pone.0052835.
   PubMed Web of Science ®Google Scholar
• Thurlow CJ, Prabaker K, Lin MY, Lolans K, Weinstein RA, Hayden MK. Anatomic sites of patient colonization and environmental contamination with Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae at long-term acute care hospitals. Infect Control Hosp Epidemiol. 2013;34(1):56–61. doi:10.1086/668783.
   PubMed Web of Science ®Google Scholar
• Korea CG, Badouraly R, Prevost MC, Ghigo JM, Beloin C. Escherichia coli K-12 possesses multiple cryptic but functional chaperone-usher fimbriae with distinct surface specificities. Environ Microbiol. 2010;12:1957–77. doi:10.1111/j.1462-2920.2010.02202.x.
   PubMed Web of Science ®Google Scholar
• Thänert R, Reske KA, Hink T, Wallace MA, Wang B, Schwartz DJ, Seiler S, Cass C, Burnham CA, Dubberke ER, et al. Comparative Genomics of Antibiotic-Resistant Uropathogens Implicates Three Routes for Recurrence of Urinary Tract Infections. mBio. 2019;10(4):e01977–19. doi:10.1128/mBio.01977-19.
   PubMed Web of Science ®Google Scholar
• Human Microbiome Project Consortium. A framework for human microbiome research. Nature. 2012;486:215–21. 7402 doi:10.1038/nature11209.
   PubMed Web of Science ®Google Scholar
• Magruder M, Sholi AN, Gong C, Zhang L, Edusei E, Huang J, Albakry S, Satlin MJ, Westblade LF, Crawford C, et al. Gut uropathogen abundance is a risk factor for development of bacteriuria and urinary tract infection. Nat Commun. 2019;10(1):5521. doi:10.1038/s41467-019-13467-w.
   PubMed Web of Science ®Google Scholar