Independent Consultant, France.
Department of Essential Medicines and Health Products, Norms and Standards for Biologicals, World Health Organization, Geneva, Switzerland.
Vaccine. 2019 Oct 3;37 Suppl 1:A99-A106. doi: 10.1016/j.vaccine.2018.11.072. Epub 2018 Dec 11.
Pre- as well as post-exposure prophylaxis plays an important role in controlling the number of deaths associated with human rabies. Rabies vaccines, classically injected intramuscularly, are now also administered by intradermal (ID) route. Vaccines to be administered by the ID route should meet the same quality, safety and efficacy specifications as vaccines for intramuscular (IM) use. The aim of this paper is to provide information based on publicly available data regarding the ID use of rabies vaccines and to identify potential needs for further analysis of the potency, immunogenicity and effectiveness of rabies vaccines administered by this route. A first literature search, focused on the immunogenicity of rabies vaccines given by ID route, identified 338 publications in the period 1997-2018, 40 of which were included in our analyses. A second search investigating the effectiveness of ID vaccination resulted in 371 hits for the period 2007-2018, of which 13 suitable publications were retained. The immunogenicity of current rabies vaccines was analyzed in 3 ways: proportion of subjects reaching the antibody threshold of 0.5 IU/ml after ID vaccination, relationship between potency and immunogenicity of the vaccine given intradermally, and comparison of antibody responses after IM or ID vaccination. Overall, vaccines administered intradermally were found immunogenic. Post-exposure prophylaxis by ID route appeared at least as immunogenic as by IM regimens. By contrast, ID pre-exposure prophylaxis trended towards lower antibody titers than IM vaccination, but the observation was not associated with any clinical relevance. Vaccine effectiveness was assessed by investigating survival after exposure. Data from more than 30,000 patients who sought rabies post-exposure prophylaxis did not indicate that current vaccines administered by ID route lack efficacy. These results support current recommendations for ID vaccination against rabies. However, published data on ID performance were associated with significant weaknesses that future research should better address.
暴露前和暴露后预防在控制与人类狂犬病相关的死亡人数方面发挥着重要作用。狂犬病疫苗，经典地肌肉内注射，现在也通过皮内（ID）途径给药。通过 ID 途径给药的疫苗应符合与肌肉内（IM）使用的疫苗相同的质量、安全性和功效规格。本文的目的是提供基于公开数据的关于狂犬病疫苗 ID 使用的信息，并确定进一步分析通过该途径给药的狂犬病疫苗效力、免疫原性和有效性的潜在需求。首次针对 ID 途径给药的狂犬病疫苗免疫原性的文献搜索，确定了 1997 年至 2018 年期间的 338 篇出版物，其中 40 篇纳入我们的分析。第二次针对 ID 接种效果的搜索导致 2007 年至 2018 年期间的 371 个结果，其中保留了 13 个合适的出版物。当前狂犬病疫苗的免疫原性通过以下 3 种方式进行分析：ID 接种后达到 0.5 IU/ml 抗体阈值的受试者比例、皮内给予的疫苗效力与免疫原性的关系，以及 IM 或 ID 接种后抗体反应的比较。总体而言，皮内给药的疫苗被发现具有免疫原性。ID 暴露后预防方案至少与 IM 方案一样具有免疫原性。相比之下，ID 暴露前预防方案的抗体滴度趋于低于 IM 接种，但观察结果与任何临床相关性无关。通过调查暴露后的存活情况评估疫苗的有效性。来自 30,000 多名寻求狂犬病暴露后预防的患者的数据表明，当前通过 ID 途径给药的疫苗并不缺乏效力。这些结果支持当前针对狂犬病的 ID 接种建议。然而，与 ID 性能相关的已发表数据存在显著弱点，未来的研究应更好地解决这些弱点。
