Infection Control Program, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland.
Epidemiology, Biostatistics and Prevention Institute, Zurich University, Zurich, Switzerland; Swiss Tropical and Public Health Institute, Basel University, Basel, Switzerland.
Lancet Infect Dis. 2017 May;17(5):528-537. doi: 10.1016/S1473-3099(17)30108-1. Epub 2017 Feb 24.
Escherichia coli infections are increasing worldwide in community and hospital settings. The E coli O-antigen is a promising vaccine target. We aimed to assess the safety and immunogenicity of a bioconjugate vaccine containing the O-antigens of four E coli serotypes (ExPEC4V).
In this multicentre phase 1b, first-in-human, single-blind, placebo-controlled trial, we randomly assigned (1:1) healthy adult women with a history of recurrent urinary tract infection (UTI) to receive a single injection of either intramuscular ExPEC4V or placebo. The primary outcome was the incidence of adverse events among vaccine and placebo recipients throughout the study. Secondary outcomes included immunogenicity and antibody functionality, and the incidence of UTIs caused by E coli vaccine serotypes in each group. This study is registered with ClinicalTrials.gov, number NCT02289794.
Between Jan 20, 2014, and Aug 27, 2014, 93 women received target-dose ExPEC4V and 95 received placebo. The vaccine was well tolerated: no vaccine-related serious adverse events occurred. Overall, 56 (60%) target-dose vaccines and 47 (49%) placebo recipients experienced at least one adverse event that was possibly, probably, or certainly related to injection. Vaccination induced significant IgG responses for all serotypes: at day 30 compared with baseline, O1A titres were 4·6 times higher, O2 titres were 9·4 times higher, O6A titres were 4·9 times higher, and O25B titres were 5·9 times higher (overall p<0·0001). Immune responses persisted at 270 days but were lower than those at 30 days. Opsonophagocytic killing activity showed antibody functionality. No reduction in the incidence of UTIs with 10 or more colony-forming units per mL of vaccine-serotype E coli was noted in the vaccine compared with the placebo group (0·149 mean episodes vs 0·146 mean episodes; p=0·522). In post-hoc exploratory analyses of UTIs with higher bacterial counts (≥10 colony-forming units per mL), the number of vaccine serotype UTIs did not differ significantly between groups (0·046 mean episodes in the vaccine group vs 0·110 mean episodes in the placebo group; p=0·074). However, significantly fewer UTIs caused by E coli of any serotype were noted in the vaccine group compared with the placebo group (0·207 mean episodes vs 0·463 mean episodes; p=0·002).
This tetravalent E coli bioconjugate vaccine candidate was well tolerated and elicited functional antibody responses against all vaccine serotypes. Phase 2 studies have been initiated to confirm these findings.
GlycoVaxyn, Janssen Vaccines.
大肠杆菌感染在社区和医院环境中在全球范围内呈上升趋势。大肠杆菌 O 抗原是一种很有前途的疫苗靶标。我们旨在评估含有四种大肠杆菌血清型（ExPEC4V）O 抗原的生物结合疫苗的安全性和免疫原性。
在这项多中心 1b 期、首次人体、单盲、安慰剂对照试验中，我们将有复发性尿路感染 (UTI) 病史的健康成年女性随机分为（1:1）肌肉内注射 ExPEC4V 或安慰剂。主要结局是研究期间疫苗和安慰剂接受者的不良事件发生率。次要结局包括免疫原性和抗体功能以及每组由大肠杆菌疫苗血清型引起的 UTI 发生率。本研究在 ClinicalTrials.gov 注册，编号为 NCT02289794。
2014 年 1 月 20 日至 2014 年 8 月 27 日，93 名女性接受了目标剂量的 ExPEC4V，95 名接受了安慰剂。疫苗耐受性良好：没有与疫苗相关的严重不良事件发生。总体而言，56 名（60%）目标剂量疫苗和 47 名（49%）安慰剂接受者经历了至少一次可能、可能或肯定与注射相关的不良事件。接种疫苗可诱导所有血清型的 IgG 产生显著反应：与基线相比，O1A 滴度高 4.6 倍，O2 滴度高 9.4 倍，O6A 滴度高 4.9 倍，O25B 滴度高 5.9 倍（总体 p<0.0001）。在 270 天时免疫反应持续存在，但低于 30 天时的反应。调理吞噬杀伤活性表明了抗体功能。与安慰剂组相比，疫苗组中每毫升 10 个或更多菌落形成单位的疫苗血清型大肠杆菌引起的 UTI 发生率没有降低（疫苗组平均 0.149 例与安慰剂组平均 0.146 例；p=0.522）。在对更高细菌计数（≥10 个菌落形成单位/毫升）的 UTI 的事后探索性分析中，两组疫苗血清型 UTI 的数量没有显著差异（疫苗组平均 0.046 例与安慰剂组平均 0.110 例；p=0.074）。然而，与安慰剂组相比，疫苗组由任何血清型大肠杆菌引起的 UTI 明显减少（疫苗组平均 0.207 例与安慰剂组平均 0.463 例；p=0.002）。
这种四价大肠杆菌生物结合疫苗候选物耐受性良好，并针对所有疫苗血清型诱导了功能性抗体反应。已启动 2 期研究以确认这些发现。
GlycoVaxyn，杨森疫苗。
