Center for Infectious Diseases, Queen Astrid Military Hospital, Brussels.
Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp.
Clin Infect Dis. 2019 Feb 1;68(4):607-614. doi: 10.1093/cid/ciy513.
The existing 4-week preexposure rabies vaccination schedule is costly and often not practicable. Shorter effective schedules would result in wider acceptance.
We conducted a noninferiority trial in 500 healthy adults comparing the safety and immunogenicity of a 2-visit (days 0 and 7) intradermal (ID) primary vaccination (2 doses of 0.1 mL ID of the human diploid cell culture rabies vaccine [HDCV] at days 0 and 7) vs a standard 3-visit schedule (single dose of 0.1 mL ID at days 0, 7, and 28). One year to 3 years after primary vaccination, a single booster dose of 0.1 mL ID of HDCV was given to evaluate the anamnestic rabies antibody response. The primary endpoint for immunogenicity was the percentage of subjects with an adequate antibody level >0.5 IU/mL 7 days after the booster injection. The safety endpoint was the proportion of participants developing adverse reactions following the primary vaccination and/or booster dose.
All subjects in both study groups possessed a rabies antibody titer >0.5 IU/mL on day 7 following the booster dose. Following the booster dose, subjects exposed to the double-dose 2-visit ID schedule had a geometric mean titer of 37 IU/mL, compared with 25 IU/mL for the single-dose 3-visit schedule (P < .001). Local reactions at the injection site following primary vaccination were mild and transient.
In healthy adults, ID administration of a double dose of 0.1 mL of HDCV over 2 visits (days 0 and 7) was safe and not inferior to the single-dose 3-visit schedule.
NCT01388985, EudraCT 2011-001612-62.
现有的 4 周暴露前狂犬病疫苗接种方案费用高昂，且往往不可行。更短的有效方案将得到更广泛的认可。
我们在 500 名健康成年人中进行了一项非劣效性试验，比较了 2 次就诊（第 0 天和第 7 天）皮内（ID）初种（在第 0 天和第 7 天给予 2 剂 0.1 毫升 ID 人二倍体细胞狂犬病疫苗[HDCV]）与标准 3 次就诊方案（在第 0、7 和 28 天给予 0.1 毫升 ID 单剂）的安全性和免疫原性。在初种后 1 年至 3 年，给予 HDCV 0.1 毫升 ID 单剂加强免疫，以评估记忆狂犬病抗体反应。免疫原性的主要终点是加强免疫后 7 天抗体水平≥0.5IU/mL 的受试者百分比。安全性终点是主要接种和/或加强剂量后出现不良反应的参与者比例。
两组研究对象在加强免疫后第 7 天均具有狂犬病抗体滴度＞0.5IU/mL。在加强免疫后，接受双剂量 2 次就诊 ID 方案的受试者几何平均滴度为 37IU/mL，而接受单剂量 3 次就诊方案的受试者为 25IU/mL（P＜0.001）。初种时注射部位的局部反应轻微且短暂。
在健康成年人中，皮内给予 0.1 毫升 HDCV 双剂量，2 次就诊（第 0 天和第 7 天），安全且不劣于单剂量 3 次就诊方案。
NCT01388985，EudraCT 2011-001612-62。
