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

Huttner, Angela; Hatz, Christoph; Dobbelsteen, Germie van den; Abbanat, Darren; Hornacek, Alena; Frölich, Rahel; Dreyer, Anita M.; Martín, Patricia A.; Davies, Todd A.; Faé, Kellen C.; Nieuwenhof, Ingrid van den; Thoelen, S; Vallière, Serge De; Kuhn, Anette; Bernasconi, Enos; Viereck, Volker; Kavvadias, Tilemachos; Kling, Kerstin; Ryu, Gloria; Hülder, Tanja; Gröger, Sabine; Scheiner, David; Alaimo, Cristina; Harbarth, Stéphan Juergen; Poolman, Jan; Fonck, Veronica Gambillara

doi:10.1016/s1473-3099(17)30108-1

Cited by 173 publications

(141 citation statements)

References 30 publications

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“…50 While some Gram-negative organisms present clinical development challenges with regard to identifying appropriate patient population with high enough disease incidence to perform prophylactic vaccine clinical studies, for a pathogen such as E coli however, patient populations can be identified and promising vaccine approaches focusing on proteins, capsular polysaccharides and lipopolysaccharides (or O antigens) are being evaluated preclinically and clinically. 67-70 …”

Section: Vaccines In Early Stages Of Development With Potential To Rementioning

confidence: 99%

The role of vaccines in fighting antimicrobial resistance (AMR)

Jansen

Anderson

2018

Human Vaccines & Immunotherapeutics

107

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The problem of antimicrobial resistance (AMR) and the associated morbidity and mortality due to antibiotic resistant bacterial pathogens is not new. However, AMR has been increasing at an alarming rate with appearances of diseases caused by bacteria exhibiting resistance to not just one but multiple classes of antibiotics. The World Health Organization (WHO) supported by governments, health ministries and health agencies has formulated global action plans to combat the rise in AMR, supporting a number of proven initiatives such as antimicrobial stewardship, investments in development of new classes of antibiotics, and educational programs designed to eliminate inappropriate antibiotic use. Vaccines as tools to reduce AMR have historically been under-recognized, yet the positive effect in reducing AMR has been well established. For example Haemophilus influenzae type B (Hib) as well as Streptococcus pneumoniae (pneumococcal) conjugate vaccines have impressive track records in not only preventing life threatening diseases caused by these bacteria, but also reducing antibiotic use and AMR. This paper will describe the drivers of antibiotic use and subsequent development of AMR; it will make the case how existing vaccines are already participating in combatting AMR, describe future prospects for the role of new vaccines in development to reduce AMR, and highlight challenges associated with future vaccine development to combat AMR.

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Section: Vaccines In Early Stages Of Development With Potential To Rementioning

confidence: 99%

The role of vaccines in fighting antimicrobial resistance (AMR)

Jansen

Anderson

2018

Human Vaccines & Immunotherapeutics

107

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“…12 In a first-in-human study conducted in women aged 18 to 70 years with a history of recurrent UTI, a single dose of ExPEC4V (4 μg PS/serotype) was found to be safe and immunogenic. 2 In the present study, the ExPEC4V vaccine was evaluated progressively from 4 μg PS/serotype to 16 μg PS/serotype since no prior safety data were available in the Japanese population. Similar to the first-in-human study, the present study showed that all ExPEC4V doses were immunogenic and well tolerated.…”

Section: Resultsmentioning

confidence: 99%

“…2 , 3 ExPEC is also a leading cause of severe sepsis, which is the 10 th overall cause of death and the 6 th leading cause of hospitalization in the United States. 4 , 5 In the US, it is estimated that up to 40,000 patients die annually due to invasive ExPEC disease (IED), in particular from E. coli sepsis.…”

Section: Introductionmentioning

confidence: 99%

“…2 , 12 Therefore, antibodies specific to O-antigen might offer effective protection against ExPEC infections. Preclinical and clinical studies have shown that multivalent conjugated E coli O-antigen vaccines are safe and immunogenic.…”

Section: Introductionmentioning

confidence: 99%

“…12 In preclinical research and in the first-in-human clinical study conducted in women with a history of recurrent UTI, ExPEC4V (4 µg Polysaccharide [PS]/serotype) was well tolerated and elicited a robust antibody response at Days 30 and 270 post-vaccination. 2 , 12 Data from Japanese Nosocomial Infections Surveillance suggest that E.coli causing bacteremia is increasing in the Japanese population. 14 Since antibiotic resistant ExPEC strains are also prevalent in the Japanese population, 15 the Phase 1 study described herein was conducted to investigate the safety, tolerability and immunogenicity of 3 different dose levels of ExPEC4V vaccine in healthy adult Japanese participants.…”

Section: Introductionmentioning

confidence: 99%

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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

Inoue

Ogawa²,

Tamura³

et al. 2018

Human Vaccines & Immunotherapeutics

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This Phase 1, randomized, double-blind, placebo-controlled study was conducted to evaluate the safety, tolerability and immunogenicity of different doses of ExPEC4V conjugate vaccine (4-16µg Polysaccharide [PS]/serotype) in healthy Japanese participants, stratified into younger (≥20 to <50 years) or older age groups (≥50 years). Within each age group, participants were randomized to a single vaccination with 1 of 3 dose levels of ExPEC4V (4, 8 and 16 µg PS/serotype) or placebo. Safety and tolerability were the primary objectives; immunogenicity was secondary. Of the 48 participants, 47 (98%) completed; one (2%) in the placebo group discontinued. A total of 48% participants had ≥1 AE (younger group: n = 13 [54%]; older group: n = 10 [41.7%]). Solicited and unsolicited AEs were reported in 44% and 8% participants, respectively in the combined ExPEC4V groups. Pain/tenderness (n = 11 [31%]) and redness (n = 9 [25%]) were the most frequently reported solicited local AEs, whereas fatigue (n = 4 [11%]), headache (n = 4 [11%]), muscle pain (n = 2 [6%]), and malaise (n = 5 [14%]) were the most common solicited systemic AEs in the combined ExPEC4V group. No serious AEs, deaths, or discontinuation due to AEs were reported. All doses were immunogenic with an increase in IgG (ELISA) geometric mean titers of at least 5-fold from baseline to Days 15 and 30 for all serotypes. Of participants vaccinated with ExPEC4V, 75% - 100% demonstrated an ELISA titer increase of ≥2-fold. Strong correlation observed between ELISA and OPK. ExPEC4V was well tolerated and elicited an immunogenic response at all dose levels (up to 16 µg PS/serotype) in healthy Japanese participants.

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