Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Vaccine. 2011 Aug 5;29(34):5666-74. doi: 10.1016/j.vaccine.2011.06.010. Epub 2011 Jun 23.
The aim of the study was to determine whether reduced doses of trivalent inactivated influenza vaccine (TIV) administered by the intradermal (ID) route generated similar immune responses to standard TIV given intramuscularly (IM) with comparable safety profiles. Recent changes in immunization recommendations have increased the number of people for whom influenza vaccination is recommended. Thus, given this increased need and intermittent vaccine shortages, means to rapidly expand the vaccine supply are needed. Previously healthy subjects 18-64 years of age were randomly assigned to one of four TIV vaccine groups: standard 15 μg HA/strain TIV IM, either 9 μg or 6 μg HA/strain of TIV ID given using a new microinjection system (BD Soluvia™ Microinjection System), or 3 μg HA/strain of TIV ID given by Mantoux technique. All vaccines contained A/New Caledonia (H1N1), A/Wyoming (H3N2) and B/Jiangsu strains of influenza. Sera were obtained 21 days after vaccination and hemagglutination inhibition (HAI) assays were performed and geometric mean titers (GMT) were compared among the groups. Participants were queried immediately following vaccination regarding injection pain and quality of the experience. Local and systemic reactions were collected for 7 days following vaccination and compared. Ten study sites enrolled 1592 subjects stratified by age; 18-49 years [N=814] and 50-64 years [N=778]. Among all subjects, for each of the three vaccine strains, the GMTs at 21 days post-vaccination for both the 9 μg and the 6 μg doses of each strain given ID were non inferior to GMTs generated after standard 15 μg doses/strain IM. However, for the 3 μg ID dose, only the A/Wyoming antigen produced a GMT that was non-inferior to the standard IM dose. Additionally, in the subgroup of subjects 50-64 years of age, the 6μg dose given ID induced GMTs that were inferior to the standard IM TIV for the A/H1N1 and B strains. No ID dose produced a GMT superior to that seen after standard IM TIV. Local erythema and swelling were significantly more common in the ID groups but the reactions were mild to moderate and short-lived. No significant safety issues related to intradermal administration were identified. Participants given TIV ID provided favorable responses to questions about their experiences with ID administration. In conclusion, for the aggregated cohorts of adults 18-64 years of age, reduced doses (6 μg and 9 μg) of TIV delivered ID using a novel microinjection system stimulated comparable HAI antibody responses to standard TIV given IM. The reduced 3 μg dose administered ID by needle and syringe, as well as the 6 μg ID for subjects aged 50-64 years of age generated poorer immune responses as compared to the 15 μg IM dose.
本研究旨在确定经皮（ID）途径给予低剂量三价灭活流感疫苗（TIV）是否与肌内（IM）给予标准 TIV 产生相似的免疫应答，且具有可比的安全性。最近免疫接种建议的改变增加了推荐接种流感疫苗的人数。因此，鉴于这种增加的需求和间歇性疫苗短缺，需要寻找快速扩大疫苗供应的方法。将 18-64 岁的健康受试者随机分配至四组 TIV 疫苗之一：标准 15 μg HA/株 TIV IM、新型微注射系统（BD Soluvia™微注射系统）给予的 9 μg 或 6 μg HA/株 TIV ID 或皮内 3 μg HA/株 TIV ID（曼陀针法）。所有疫苗均含有 A/New Caledonia（H1N1）、A/Wyoming（H3N2）和 B/Jiangsu 流感株。接种后 21 天采集血清，进行血凝抑制（HAI）检测，并比较各组的几何平均滴度（GMT）。接种后立即询问参与者关于注射疼痛和体验质量的问题。接种后 7 天内收集局部和全身反应并进行比较。十个研究地点按年龄分层共纳入 1592 名受试者；18-49 岁[N=814]和 50-64 岁[N=778]。在所有受试者中，对于三种疫苗株，每种菌株的 9 μg 和 6 μg ID 剂量接种后 21 天的 GMT 与标准 15 μg 剂量/株 IM 生成的 GMT 相当。然而，对于 3 μg ID 剂量，只有 A/Wyoming 抗原产生的 GMT 与标准 IM 剂量相当。此外，在 50-64 岁年龄组的亚组中，ID 给予的 6μg 剂量引起的 GMT 低于标准 IM TIV 对 A/H1N1 和 B 株的 GMT。没有 ID 剂量产生的 GMT 优于标准 IM TIV 后的 GMT。局部红斑和肿胀在 ID 组中更为常见，但反应为轻度至中度和短暂。未发现与皮内给药相关的严重安全问题。接受 TIV ID 接种的受试者对 ID 接种体验相关问题的回答表示满意。总之，对于 18-64 岁的成年人群体，新型微注射系统给予的低剂量（6 μg 和 9 μg）TIV 皮内接种可刺激与肌内标准 TIV 相当的 HAI 抗体应答。与 15 μg IM 剂量相比，经皮针和注射器给予的 3 μg 低剂量以及 50-64 岁受试者的 6 μg ID 产生的免疫应答较差。
