Queen Savabha Memorial Institute (WHO Collaborating Center for Research on Rabies Pathogenesis and Prevention), Thai Red Cross Society, Thailand.
Vaccine. 2013 Mar 25;31(13):1748-51. doi: 10.1016/j.vaccine.2013.01.035. Epub 2013 Jan 29.
Pre-exposure prophylaxis is recommended for people who will be exposed to rabies virus in the laboratory or who will contact with mammals. World Health Organization recommends 2 doses of a cell-culture rabies vaccine given 1 week apart, and a third booster dose given 2-3 weeks later. Neutralizing antibody response is virtually 100%, and the individual remains sensitized indefinitely. Intradermal pre-exposure regimen for rabies prophylaxis is more economical compared with the conventional intramuscular regimen in terms of vaccine volume. However, both regimens require three clinic visits. In order to reduce non-medical expenses such as transportation to the clinics and to increase compliance, the immunogenicity and safety of two-visit intradermal regimen for pre-exposure prophylaxis were studied. Fifty-five healthy subjects aged between 18 and 24 years were enrolled and divided into two groups. Group A (n=39) received 0.1 ml of purified Vero cell rabies vaccine (PVRV; Sanofi Pasteur, Lyon, France; Lot no. Z0996 with an antigenic value of 4.8 IU/0.5 ml vial) intradermally each at two sites on days 0 and 21. Group B (n=16) received 0.5 ml of PVRV intramuscularly on days 0, 7 and 21, as conventional intramuscular regimen for pre-exposure prophylaxis. Rabies neutralizing antibody (Nab) titers were measured on days 0, 35, 365 and 379 (14 days after simulated post-exposure booster vaccination). All subjects from two groups had Nab titers ≥0.5 IU/ml on day 35. In addition, the difference between geometric mean titers for group A (4.51 IU/ml; range of Nab titers 1.69-13.0 IU/ml) and group B (6.74 IU/ml; range of Nab titers 2.20-14.23 IU/ml) on day 35 was not statistically significant (p>0.05). One year after pre-exposure vaccination, all subjects in both groups received simulated post-exposure booster vaccination with 0.1 ml of PVRV ID on days 0 and 3 (day 365 and day 368 after pre-exposure vaccination). After simulated booster vaccinations with 0.1 ml PVRV ID on days 0 and 3, all subjects in groups A (GMT 14.38 IU/ml; range 2.99-308.44 IU/ml) and in group B (GMT 14.06 IU/ml; range 3.12-62.09 IU/ml) had rabies Nab titers ≥0.5 IU/ml on day 14 post-booster (p>0.05). Mild local adverse events such as pain at injection site, pruritus and erythema were observed. Our study indicated that 2-site intradermal pre-exposure regimen on days 0 and 21 with 0.1 ml of cell-culture rabies vaccine is safe and immunogenic as the conventional intramuscular regimen.
暴露前预防适用于将在实验室接触狂犬病病毒的人或接触哺乳动物的人。世界卫生组织建议，使用细胞培养狂犬病疫苗，在第 1 周和第 4 周分别接种 2 剂，然后在第 2-3 周再接种第 3 剂加强针。中和抗体反应几乎达到 100%，并且个体可以无限期地保持致敏状态。与传统的肌肉内方案相比，皮内暴露前预防方案的狂犬病疫苗量更经济。然而，两种方案都需要 3 次就诊。为了减少前往诊所的非医疗费用，并提高依从性，研究了两剂皮内方案用于暴露前预防的免疫原性和安全性。将 55 名年龄在 18-24 岁之间的健康受试者分为两组。A 组（n=39）在第 0 天和第 21 天在两个部位各皮内注射 0.1 毫升纯化 Vero 细胞狂犬病疫苗（PVRV；赛诺菲巴斯德，里昂，法国；Lot no. Z0996，抗原值为 4.8 IU/0.5 ml 小瓶）。B 组（n=16）在第 0、7 和 21 天分别肌肉内注射 0.5 毫升 PVRV，作为传统的肌肉内暴露前预防方案。在第 0、35、365 和 379 天（模拟暴露后加强接种后 14 天）测量狂犬病中和抗体（Nab）滴度。两组所有受试者在第 35 天均具有≥0.5 IU/ml 的 Nab 滴度。此外，第 35 天 A 组（4.51 IU/ml；Nab 滴度范围为 1.69-13.0 IU/ml）和 B 组（6.74 IU/ml；Nab 滴度范围为 2.20-14.23 IU/ml）的几何平均滴度之间的差异无统计学意义（p>0.05）。暴露前接种疫苗 1 年后，两组所有受试者均在第 0 和第 3 天（暴露前接种后第 365 天和第 368 天）接受 0.1 毫升 PVRV ID 的模拟暴露后加强接种。在第 0 和第 3 天接受 0.1 毫升 PVRV ID 模拟加强接种后，A 组（GMT 14.38 IU/ml；Nab 滴度范围 2.99-308.44 IU/ml）和 B 组（GMT 14.06 IU/ml；Nab 滴度范围 3.12-62.09 IU/ml）的所有受试者在加强接种后第 14 天均具有≥0.5 IU/ml 的狂犬病 Nab 滴度（p>0.05）。观察到轻微的局部不良反应，如注射部位疼痛、瘙痒和红斑。我们的研究表明，在第 0 天和第 21 天使用 0.1 毫升细胞培养狂犬病疫苗进行 2 部位皮内暴露前预防方案是安全且具有免疫原性的，与传统的肌肉内方案相当。
