Chioato A, Noseda E, Felix S D, Stevens M, Del Giudice G, Fitoussi S, Kleinschmidt A
Novartis Institutes for BioMedical Research, Translational Science, CH-4002 Basel, Switzerland.
Clin Vaccine Immunol. 2010 Dec;17(12):1952-7. doi: 10.1128/CVI.00175-10. Epub 2010 Oct 20.
The objective of this study was to evaluate the efficacy of influenza and meningococcal vaccines in healthy subjects exposed to the anti-interleukin-1β (anti-IL-1β) monoclonal antibody canakinumab. This was an open-label, parallel group, randomized, single-center study of healthy subjects (aged 18 to 45 years). At baseline, antibody (Ab) titers were measured and subjects were randomized (1:1) to a single 300-mg canakinumab dose administered subcutaneously (s.c.) or received no treatment (control group). After 2 weeks, subjects were treated with inactivated, unadjuvanted influenza and conjugated group C meningococcal (MenC) vaccines, administered intramuscularly (i.m.). The primary efficacy variable was the response (≥ 2-fold increase in Ab titer in ≥ 2 of 3 influenza virus strains) after 4 weeks in subjects treated with canakinumab compared to the control group. Secondary efficacy variables were the antibody response to vaccines at different thresholds and time points. Fifty-one of 112 subjects screened were randomized to canakinumab (n = 25) or the control group (n = 26). Antibody responses to vaccinations measured against different influenza virus strains and one MenC strain at 4 weeks were comparable in the canakinumab and control groups. The primary efficacy variable, the response to influenza vaccination (≥ 2-fold increase in Ab titer in ≥ 2 of 3 serotypes) at 4 weeks, was shown in 24/25 subjects in the canakinumab group compared to 25/25 subjects in the control group. Antibody responses remained comparable in the two groups at the different time points assessed. Headache was the most frequently reported adverse event. No deaths or serious adverse events were reported during the study. We concluded that a single dose of 300 mg canakinumab s.c. does not affect the induction or persistence of antibody responses after vaccination with unadjuvanted influenza or alum-adjuvanted MenC vaccines in healthy subjects.
本研究的目的是评估流感疫苗和脑膜炎球菌疫苗在接受抗白细胞介素-1β(抗IL-1β)单克隆抗体卡那单抗治疗的健康受试者中的疗效。这是一项针对健康受试者(年龄在18至45岁之间)的开放标签、平行组、随机、单中心研究。在基线时,测量抗体(Ab)滴度,受试者被随机(1:1)分为皮下注射(s.c.)一剂300 mg卡那单抗或不接受治疗(对照组)。2周后,受试者接受肌内注射(i.m.)的灭活、无佐剂流感疫苗和结合C群脑膜炎球菌(MenC)疫苗治疗。主要疗效变量是与对照组相比,接受卡那单抗治疗的受试者在4周后对疫苗的反应(三种流感病毒株中至少两种的Ab滴度增加≥2倍)。次要疗效变量是在不同阈值和时间点对疫苗的抗体反应。112名筛查受试者中的51名被随机分为卡那单抗组(n = 25)或对照组(n = 26)。在卡那单抗组和对照组中,4周时针对不同流感病毒株和一种MenC株测量的疫苗接种抗体反应相当。主要疗效变量,即4周时对流感疫苗接种的反应(三种血清型中至少两种的Ab滴度增加≥2倍),在卡那单抗组的24/25名受试者中出现,而对照组为25/25名受试者。在评估的不同时间点,两组的抗体反应仍然相当。头痛是最常报告的不良事件。研究期间未报告死亡或严重不良事件。我们得出结论,一剂300 mg皮下注射卡那单抗不会影响健康受试者接种无佐剂流感疫苗或明矾佐剂MenC疫苗后抗体反应的诱导或持续存在。