Merck & Co, Kenilworth, NJ, USA.
Merck & Co, Kenilworth, NJ, USA.
Lancet Infect Dis. 2016 Aug;16(8):915-22. doi: 10.1016/S1473-3099(16)00133-X. Epub 2016 Apr 6.
The licensed live, attenuated varicella-zoster virus vaccine prevents herpes zoster in adults older than 50 years. We aimed to determine whether intradermal administration of zoster vaccine could enhance vaccine immunogenicity compared with conventional needle subcutaneous administration.
In this randomised, dose-ranging study, adults aged 50 years or older who had a history of varicella or who had resided in a country with endemic varicella-zoster virus infection for 30 years or more were eligible. Participants received the approved full or a 1/3 dose of zoster vaccine given subcutaneously or one of four intradermal doses (full, 1/3, 1/10, or 1/27 dose) using the MicronJet600 device. The two subcutaneous doses and the four intradermal doses were randomised (1·5:1:1:1:1:1) by computer generated sequence with randomisation stratified by age (50-59 years or 60 years or older). The primary immunogenicity endpoint was the change from baseline in IgG antibody to varicella-zoster virus-specific glycoproteins (gpELISA) measured at 6 weeks. All patients were included in the primary and safety analyses. This study is registered with ClinicalTrials.gov, number NCT01385566.
Between Sept 2, 2011, and Jan 13, 2012, 224 participants were enrolled from three clinics in the USA and 223 were randomly assigned: 52 to receive the full dose subcutaneous zoster vaccine, 34 to receive the 1/3 dose subcutaneous zoster vaccine, 34 to receive the full dose intradermal zoster vaccine, 35 to receive the 1/3 dose intradermal zoster vaccine, 34 to receive the 1/10 dose intradermal zoster vaccine, and 34 to receive the 1/27 dose intradermal zoster vaccine. Full dose zoster vaccine given subcutaneously resulted in a gpELISA geometric mean fold-rise (GMFR) of 1·74 (90% CI 1·48-2·04) at 6 weeks post-vaccination compared with intradermal administration which resulted in a significantly higher gpELISA GMFR of 3·25 (2·68-3·94; p<0·0001), which also remained high at 18 months. An apparent dose-response relation was observed with intradermal administration (1/3 dose subcutaneous GMFR 1·64 [90% CI 1·36-1·99], 1/3 dose intradermal 2·58 (2·13-3·13), 1/10 dose intradermal 2·22 [1·83-2·69], and 1/27 dose intradermal 1·64 [1·35-2·00]). Each partial dose of zoster vaccine given intradermaly had a gpELISA GMFR comparable to that of full dose zoster vaccine given subcutaneously. Transient erythema and induration were more common after intradermal administration (31% erythema for full subcutaneous dose and 77% for intradermal dose).
Intradermal zoster vaccine showed a greater increase in varicella-zoster virus gpELISA antibody compared with subcutaneous zoster vaccine at comparable doses. Larger and longer studies of intradermal administration of live, attenuated zoster vaccine are needed to provide convincing evidence of improved cell mediated immunity.
Merck & Co Inc.
经许可的减毒活水痘带状疱疹病毒疫苗可预防 50 岁以上成年人的带状疱疹。我们旨在确定与传统的皮下注射相比，水痘带状疱疹疫苗的皮内给药是否可以增强疫苗的免疫原性。
在这项随机、剂量范围研究中，年龄在 50 岁或以上、有过水痘史或在水痘带状疱疹病毒流行的国家居住 30 年或以上的成年人有资格参加。参与者接受批准的全剂量或三分之一剂量的带状疱疹疫苗皮下注射，或使用 MicronJet600 设备接受四种皮内剂量（全剂量、三分之一剂量、十分之一剂量或二十七分之一剂量）之一。两种皮下剂量和四种皮内剂量通过计算机生成的序列随机分配（1.5:1:1:1:1:1），并按年龄分层（50-59 岁或 60 岁或以上）进行随机化。主要免疫原性终点是在 6 周时测量的针对水痘带状疱疹病毒特异性糖蛋白（gpELISA）的 IgG 抗体与基线相比的变化。所有患者均纳入主要和安全性分析。这项研究在 ClinicalTrials.gov 注册，编号为 NCT01385566。
2011 年 9 月 2 日至 2012 年 1 月 13 日，从美国的三个诊所招募了 224 名参与者，并随机分配了 223 名：52 名接受全剂量皮下带状疱疹疫苗，34 名接受三分之一剂量皮下带状疱疹疫苗，34 名接受全剂量皮内带状疱疹疫苗，35 名接受三分之一剂量皮内带状疱疹疫苗，34 名接受十分之一剂量皮内带状疱疹疫苗，34 名接受二十七分之一剂量皮内带状疱疹疫苗。与皮内给药相比，皮下给予全剂量带状疱疹疫苗导致 gpELISA 几何平均倍数增加（GMFR）在接种疫苗后 6 周时为 1.74（90%CI 1.48-2.04），而皮内给药则导致 gpELISA GMFR 显著更高，为 3.25（2.68-3.94；p<0.0001），在 18 个月时仍然很高。在皮内给药时观察到明显的剂量反应关系（三分之一剂量皮下 GMFR 为 1.64（90%CI 1.36-1.99），三分之一剂量皮内 2.58（2.13-3.13），十分之一剂量皮内 2.22（1.83-2.69），二十七分之一剂量皮内 1.64（1.35-2.00））。每种皮内给予的部分带状疱疹疫苗的 gpELISA GMFR与皮下给予的全剂量带状疱疹疫苗相当。皮内给药后，红斑和硬结更常见（全皮下剂量为 31%，皮内剂量为 77%）。
与皮下带状疱疹疫苗相比，皮内带状疱疹疫苗显示出更大幅度的水痘带状疱疹病毒 gpELISA 抗体增加，在可比剂量下。需要进行更大规模和更长时间的皮内活减毒带状疱疹疫苗接种研究，以提供对细胞介导免疫改善的令人信服的证据。
默克公司。
