Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Center of Excellence for Pediatric Infectious Diseases and Vaccines, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Center of Excellence for Pediatric Infectious Diseases and Vaccines, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Thai Red Cross Emerging Infectious Diseases Clinical Center (TRC-EID), King Chulalongkorn Memorial Hospital, Bangkok, Thailand.
Vaccine. 2019 Aug 23;37(36):5307-5313. doi: 10.1016/j.vaccine.2019.07.055. Epub 2019 Jul 26.
World Health Organization changed the recommendation for pre-exposure rabies prophylaxis from 3-dose to 2-dose regimen in 2018. Given limited data of 2-dose regimens in pediatric population, this study aimed to compare the immunogenicity between 2-dose and 3-dose pre-exposure rabies immunization.
This study was conducted among healthy children aged 2-12 years. They were randomized to 2-dose vaccination (2D) on days 0 and 28 or 3-dose vaccination (3D) on days 0, 7, and 28. Purified Vero cell rabies vaccine (PVRV-Verorab™) was administered intramuscularly. Rabies virus neutralizing antibody (RVNA) titers were measured at 3 time points: 14-day after complete vaccination, 1-year pre-booster vaccination, and 7-day post-booster dose to mimic scenario of rabies exposure. RVNA titers ≥0.5 IU/ml were considered adequate antibody. T cell specific response to rabies vaccine antigen was measured using the interferon-gamma enzyme linked immunospot assay.
From September to October 2017, 107 participants (51% males), 78 in 2D group and 29 in 3D group were enrolled. Median age was 5.8 years (IQR 4.4-7.3). All participants had RVNA titers ≥0.5 IU/ml after primary vaccination [GMT 2D: 18.6 (95%CI 15.9-21.8) and 3D: 16.3 (95%CI 13.2-20.1 IU/ml), p = 0.35]. At 1-year prior to receiving the booster, only 80% of the children in 2D group maintained RVNA titers ≥0.5 IU/ml compared to 100% of the children in 3D group (p = 0.01). However, all participants in both groups had RVNA ≥0.5 IU/ml at 7-day post booster vaccination [GMT 2D: 20.9 (95%CI 17.4-25.3) and 3D: 22.2 (95%CI 15.8-31.4) IU/ml (P = 0.75)]. The median number of IFN-γ secreting cells at 7-day post-booster dose was 98 and 128 SFCs per 10 PBMCs in the 2D and 3D groups, respectively (P = 0.30).
Two-dose primary rabies immunization provided adequate antibody at post primary vaccination and post booster. The results support 2-dose regimen of pre-exposure rabies immunization in the pediatric population.
世界卫生组织在 2018 年将狂犬病暴露前预防的推荐方案从 3 针改为 2 针。鉴于儿童人群中 2 针方案的数据有限，本研究旨在比较 2 针和 3 针暴露前狂犬病免疫的免疫原性。
本研究在 2-12 岁的健康儿童中进行。他们被随机分为 2 剂接种（2D）组，在第 0 天和第 28 天接种，或 3 剂接种（3D）组，在第 0、7 和 28 天接种。狂犬病纯化vero 细胞疫苗（PVRV-Verorab™）肌肉注射。在 3 个时间点测量狂犬病病毒中和抗体（RVNA）滴度：完全接种后 14 天、预加强接种前 1 年和加强接种后 7 天，以模拟狂犬病暴露的情况。RVNA 滴度≥0.5 IU/ml 被认为是足够的抗体。使用干扰素-γ酶联免疫斑点测定法测量针对狂犬病疫苗抗原的 T 细胞特异性反应。
2017 年 9 月至 10 月，共纳入 107 名参与者（男性 51%），2D 组 78 名，3D 组 29 名。中位年龄为 5.8 岁（四分位距 4.4-7.3）。所有参与者在初次接种后均有 RVNA 滴度≥0.5 IU/ml[GMT 2D：18.6（95%CI 15.9-21.8）和 3D：16.3（95%CI 13.2-20.1 IU/ml），p=0.35]。在接受加强针前 1 年，只有 2D 组的 80%儿童维持 RVNA 滴度≥0.5 IU/ml，而 3D 组的 100%儿童维持 RVNA 滴度≥0.5 IU/ml（p=0.01）。然而，两组所有参与者在加强针后 7 天均有 RVNA≥0.5 IU/ml[GMT 2D：20.9（95%CI 17.4-25.3）和 3D：22.2（95%CI 15.8-31.4）IU/ml（P=0.75）]。加强针后 7 天，2D 组和 3D 组 IFN-γ分泌细胞的中位数分别为每 10 PBMCs 98 和 128 个 SFC（P=0.30）。
2 剂基础狂犬病免疫在基础免疫和加强免疫后提供了足够的抗体。结果支持在儿童人群中使用狂犬病暴露前免疫的 2 针方案。
