Diez-Domingo Javier, Weinke Thomas, Garcia de Lomas Juan, Meyer Claudius U, Bertrand Isabelle, Eymin Cécile, Thomas Stéphane, Sadorge Christine
FISABIO-Public Health, Avda Cataluna 21, 46020 Valencia, Spain; Universidad Católica de Valencia, 'San Vicente Martir', Valencia, Spain.
Klinikum Ernst von Bergmann, Charlottenstr. 72, 14467 Potsdam, Germany.
Vaccine. 2015 Feb 4;33(6):789-95. doi: 10.1016/j.vaccine.2014.12.024. Epub 2014 Dec 30.
Zostavax(®) is a live, attenuated varicella zoster virus (VZV) vaccine developed specifically for the prevention of HZ and PHN in individuals aged ≥50 years. During the clinical development of Zostavax, which was mainly in the US, the vaccine was administrated by the subcutaneous (SC) route. In Europe, many healthcare professionals prefer administering vaccines by the intramuscular (IM) route. This was an open-label, randomised trial conducted in 354 subjects aged ≥50 years. The primary objectives were to demonstrate that IM administration is both non-inferior to SC administration in terms of 4-week post-vaccination geometric mean titres (GMTs), and elicits an acceptable geometric mean fold-rise (GMFR) of antibody titres measured by glycoprotein enzyme-linked immunosorbent assay. Pre-specified non-inferiority was set as the lower bound of the 95% confidence interval (CI) of the GMT ratio (IM/SC) being >0.67. An acceptable GMFR for the IM route was pre-specified as the lower bound of its 95% CI being >1.4. Description of the VZV immune response using the interferon-gamma enzyme-linked immunospot (IFN-γ ELISPOT) assay and of the safety were secondary objectives. Participants were randomised to IM or SC administration (1:1). The baseline demographics were comparable between groups; mean age: 62.6 years (range: 50.0-90.5). The primary immunogenicity objectives were met (per protocol analysis): GMT ratio (IM/SC): 1.05 (95% CI: 0.93-1.18); GMFR: 2.7 (2.4-3.0). VZV immune response using IFN-γ ELISPOT were comparable between groups. Frequencies of systemic adverse events were comparable between groups. Injection-site reactions were less frequent with IM than SC route: erythema (15.9% versus 52.5%), pain (25.6% versus 39.5%) and swelling (13.6% versus 37.3%), respectively. In adults aged ≥50 years, IM administration of Zostavax elicited similar immune responses to SC administration and was well tolerated, with fewer injection-site reactions than with SC administration.
重组带状疱疹疫苗（Zostavax®）是一种减毒活水痘带状疱疹病毒（VZV）疫苗，专门用于预防50岁及以上人群的带状疱疹（HZ）和带状疱疹后神经痛（PHN）。在主要在美国进行的Zostavax临床开发过程中，该疫苗通过皮下（SC）途径给药。在欧洲，许多医疗保健专业人员更倾向于通过肌肉内（IM）途径接种疫苗。这是一项在354名50岁及以上受试者中进行的开放标签随机试验。主要目标是证明在接种疫苗后4周的几何平均滴度（GMT）方面，肌肉内注射在非劣效于皮下注射，并且通过糖蛋白酶联免疫吸附测定法测量的抗体滴度几何平均倍数升高（GMFR）是可接受的。预先设定的非劣效性为GMT比值（IM/SC）的95%置信区间（CI）下限>0.67。肌肉内途径可接受的GMFR预先设定为其95%CI下限>1.4。使用干扰素-γ酶联免疫斑点（IFN-γ ELISPOT）测定法描述VZV免疫反应以及安全性是次要目标。参与者被随机分配至肌肉内或皮下注射（1:1）。两组之间的基线人口统计学特征具有可比性；平均年龄：62.6岁（范围：50.0 - 90.5）。达到了主要免疫原性目标（按方案分析）：GMT比值（IM/SC）：1.05（95%CI：0.93 - 1.18）；GMFR：2.7（2.4 - 3.0）。两组之间使用IFN-γ ELISPOT测定法的VZV免疫反应具有可比性。两组之间全身不良事件的发生率具有可比性。肌肉内注射部位反应的发生率低于皮下注射途径：红斑（分别为15.9%对52.5%）、疼痛（25.6%对39.5%）和肿胀（13.6%对37.3%）。在50岁及以上的成年人中，Zostavax肌肉内注射引发的免疫反应与皮下注射相似，并且耐受性良好，注射部位反应比皮下注射少。
