Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Centre for Pharmaceutical Research, Kansas City, MO, USA.
Lancet Infect Dis. 2019 Jun;19(6):631-640. doi: 10.1016/S1473-3099(18)30803-X. Epub 2019 May 9.
ExPEC4V (JNJ-63871860) is a bioconjugate vaccine, containing O-antigens from Escherichia coli serotypes O1A, O2, O6A, and O25B, developed for the prevention of invasive extra-intestinal pathogenic E coli (ExPEC) disease. We aimed to assess safety, reactogenicity, and immunogenicity of ExPEC4V in healthy adults.
In this phase 2 randomised, double-blind placebo-controlled study, we recruited healthy adults (≥18 years with a body-mass index of 35 kg/m or less) between Nov 16, 2015, and Aug 8, 2017, and randomly assigned them to receive a single dose of ExPEC4V (antigen O1A:O2:O6A:O25B content 4:4:4:4 μg [group 1]; 4:4:4:8 μg [group 2], 8:8:8:8 μg [group 3], 8:8:8:16 μg [group 4], or 16:16:16:16 μg [group 5]) or placebo. The primary objectives were evaluation of the safety, tolerability, and immunogenicity of ExPEC4V and determination of its dose-dependent immunogenicity 15 days after vaccination by ELISA in individuals who had received at least one vaccination dose. Antibody titres and safety evaluation were used to select two ExPEC4V doses for assessment up to day 360. This trial is registered at ClinicalTrials.gov, number NCT02546960.
Of 848 enrolled participants, 843 (99%) received the ExPEC4V vaccine (757) or placebo (86) and were included in the safety analysis. Of 757 participants vaccinated with ExPEC4V, 222 (29%) had a solicited local adverse event and 325 (43%) had any solicited systemic adverse event, compared with 11 (13%) and 30 (35%) of 86 participants in the control group. Symptoms were mild-to-moderate. The most frequently reported solicited local adverse event was pain or tenderness (205 [27·1%] of 757 in combined ExPEC4V groups) and the most frequently reported solicited systemic adverse event was fatigue (208 [27·6%] of 757). Only 13 (2%) of 843 had a grade 3 event. At day 15, 80% or more of all participants achieved a two times or greater increase in serotype-specific IgG antibodies (except O25B at the lowest dose, 103 [72%] of 144). At day 360, 66% (95% CI 56·47-74·33) of participants in group 2 and 71% (62·13-78·95) of participants in group 4 selected for long-term follow-up maintained a two times or greater increase in serotype-specific antibody compared with baseline.
EXPEC4V seemed well tolerated and elicited robust and functional antibody responses across all serotypes, doses, and age groups. For the two dosages evaluated (4:4:4:8 μg and 8:8:8:16 μg), the immune response persisted for 1 year.
Janssen Pharmaceuticals.
ExPEC4V（JNJ-63871860）是一种生物偶联疫苗，包含大肠杆菌血清型 O1A、O2、O6A 和 O25B 的 O 抗原，用于预防侵袭性肠道外致病性大肠杆菌（ExPEC）疾病。我们旨在评估 ExPEC4V 在健康成年人中的安全性、反应原性和免疫原性。
在这项 2 期随机、双盲、安慰剂对照研究中，我们招募了健康成年人（年龄≥18 岁，体重指数为 35kg/m 或以下），于 2015 年 11 月 16 日至 2017 年 8 月 8 日之间进行随机分组，接受单剂量 ExPEC4V（抗原 O1A：O2：O6A：O25B 含量 4：4：4：4μg[第 1 组]；4：4：4：8μg[第 2 组]，8：8：8：8μg[第 3 组]，8：8：8：16μg[第 4 组]或 16：16：16：16μg[第 5 组]）或安慰剂。主要目的是评估 ExPEC4V 的安全性、耐受性和免疫原性，并在接种至少一剂疫苗后 15 天通过 ELISA 确定其剂量依赖性免疫原性。抗体滴度和安全性评估用于选择两种 ExPEC4V 剂量进行评估，直至第 360 天。该试验在 ClinicalTrials.gov 注册，编号为 NCT02546960。
在 848 名入组的参与者中，843 名（99%）接受了 ExPEC4V 疫苗（757 名）或安慰剂（86 名），并纳入安全性分析。在接受 ExPEC4V 疫苗的 757 名参与者中，222 名（29%）有局部不良反应，325 名（43%）有任何全身不良反应，而对照组中 86 名参与者中分别有 11 名（13%）和 30 名（35%）有此类反应。症状为轻度至中度。最常报告的局部不良反应是疼痛或压痛（205 例[27.1%]，联合 ExPEC4V 组），最常报告的全身不良反应是疲劳（208 例[27.6%]，联合 ExPEC4V 组）。843 名参与者中只有 13 名（2%）出现了 3 级事件。在第 15 天，所有参与者中有 80%或更多的人血清型特异性 IgG 抗体增加了两倍或以上（最低剂量 O25B 除外，144 例中有 103 例[72%]）。在第 360 天，在 2 组中选择进行长期随访的参与者中，66%（95%CI 56.47-74.33）和 4 组中 71%（62.13-78.95）的参与者保持了血清型特异性抗体增加两倍或以上与基线相比。
ExPEC4V 似乎耐受性良好，可引起所有血清型、剂量和年龄组的强烈和功能性抗体反应。对于评估的两种剂量（4：4：4：8μg 和 8：8：8：16μg），免疫反应持续了 1 年。
杨森制药公司。
