Fierro Carlos A, Sarnecki Michal, Doua Joachim, Spiessens Bart, Go Oscar, Davies Todd A, van den Dobbelsteen Germie, Poolman Jan, Abbanat Darren, Haazen Wouter
Johnson County Clin-Trials, Lenexa, Kansas, USA.
Infectious Diseases and Vaccines, Janssen Research and Development, Janssen Vaccines, Bern, Switzerland.
Open Forum Infect Dis. 2023 Aug 11;10(8):ofad417. doi: 10.1093/ofid/ofad417. eCollection 2023 Aug.
ExPEC10V is a bioconjugate vaccine containing O-antigen polysaccharides of 10 extraintestinal pathogenic (ExPEC) serotypes. This phase 1/2a study (NCT03819049) assessed the safety, reactogenicity, and immunogenicity of ExPEC10V (VAC52416) to prevent invasive disease in elderly adults.
The observer-blind, active-controlled design included a 28-day screening, vaccination, 181-day follow-up, and 1-year follow-up. Participants (60-85 years of age) were randomized to ExPEC10V low dose (antigen dose range, 4-8 µg), ExPEC10V medium dose (4-16 µg), or ExPEC10V high dose (8-16 µg); 4-valent ExPEC vaccine (ExPEC4V); or 13-valent pneumococcal conjugate vaccine (PCV13). The incidence of adverse events (AEs; solicited, day 15; unsolicited, day 30; serious AEs, day 181) and immunogenicity (electrochemiluminescent-based assay [ECL] and multiplex opsonophagocytic assay [MOPA]) were assessed. Optimal ExPEC10V dose was determined from safety data through day 30 and an immunogenicity dose selection algorithm based on day 15 ECL and MOPA results.
A total of 416 participants were included (median age, 64.0 years; 54.8% female). The incidences of solicited local and systemic AEs were, respectively, 44.2% and 39.4% for low-dose, 52.9% and 46.1% for medium-dose, 57.7% and 45.2% for high-dose ExPEC10V, and 74.1% and 48.1% for PCV13. Five serious AEs, not vaccine related, were reported. The ECL revealed a robust antibody response to ExPEC10V through year 1. Opsonophagocytic killing activity was detected against all but serotype O8; this lack of response against serotype O8 was linked to low assay sensitivity. Based on the totality of data, high-dose ExPEC10V was considered optimal.
ExPEC10V was well tolerated and immunogenic in elderly adults against all but serotype O8.
ExPEC10V是一种生物共轭疫苗，含有10种肠外致病性（ExPEC）血清型的O抗原多糖。这项1/2a期研究（NCT03819049）评估了ExPEC10V（VAC52416）预防老年人侵袭性疾病的安全性、反应原性和免疫原性。
采用观察者盲法、活性对照设计，包括28天的筛查、疫苗接种、181天的随访和1年的随访。参与者（60 - 85岁）被随机分为ExPEC10V低剂量组（抗原剂量范围为4 - 8μg）、ExPEC10V中剂量组（4 - 16μg）或ExPEC10V高剂量组（8 - 16μg）；4价ExPEC疫苗（ExPEC4V）；或13价肺炎球菌结合疫苗（PCV13）。评估不良事件（AE；主动报告，第15天；非主动报告，第30天；严重AE，第181天）的发生率和免疫原性（基于电化学发光的检测方法[ECL]和多重调理吞噬检测方法[MOPA]）。根据第30天的安全性数据和基于第15天ECL和MOPA结果的免疫原性剂量选择算法确定ExPEC10V的最佳剂量。
共纳入416名参与者（中位年龄64.0岁；54.8%为女性）。ExPEC10V低剂量组主动报告的局部和全身AE发生率分别为44.2%和39.4%，中剂量组分别为52.9%和46.1%，高剂量组分别为57.7%和45.2%，PCV13组分别为至74.1%和48.1%。报告了5例与疫苗无关的严重AE。ECL显示在第1年期间对ExPEC10V有强烈的抗体反应。除O8血清型外，对所有血清型均检测到调理吞噬杀伤活性；对O8血清型缺乏反应与检测灵敏度低有关。基于全部数据，高剂量ExPEC10V被认为是最佳的。
ExPEC10V在老年人中耐受性良好，除O8血清型外，对其他血清型均具有免疫原性。
