BACKGROUND Trials assessing the safety of novel vaccine candidates are essential in the evaluation and development of candidate vaccines. Immunogenicity and dose-sparing features of vaccination approaches which target skin and associated tissues have garnered increased interest; for enteric vaccines, cutaneous vaccination has been of particular interest. Cutaneous vaccine site reactions are among the most common and visible vaccine related adverse events (AEs) when skin routes are used. Regulatory guidelines governing classification of severity focus on functional impact but are insufficient to characterize a spectrum of skin reaction and allow for comparisons of routes, doses and products with similar local cutaneous AEs. OBJECTIVES Our group developed a grading scale to evaluate and compare cutaneous vaccine site reactions ahead of early-phase clinical trials of intradermal (ID) and transcutaneous immunization (TCI) with enterotoxigenic E.coli (ETEC) vaccine candidates (adhesin-based vaccine co-administered with LTR192G). We reviewed existing methods for characterizing the appearance and severity of local vaccine site reactions following TCI and ID vaccination and devised a standardized vaccine site appearance grading scale (VSAGS) for use in the clinical development of novel ETEC vaccine candidates which focused on pathophysiologic manifestation of skin findings. RESULTS Available data from published reports revealed erythematous papules and pruritus were the most common local AEs associated with TCI. Frequency of reactions varied notably across studies as did TCI vaccination methodologies and products. ID vaccination commonly results in erythema and induration at the vaccine site as well as pigmentation changes. There was no published methodology to characterize the spectrum of dermatologic findings. CONCLUSION ID and TCI vaccination are associated with a largely predictable range of cutaneous AEs. A grading scale focused on the appearance of cutaneous changes was useful in comparing cutaneous AEs. A standardized grading scale will facilitate documentation and comparison of cutaneous AEs.

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开发了用于局部皮肤反应的分级系统，用于皮内和经皮ETEC疫苗的临床试验。

背景技术评估新疫苗候选物的安全性的试验对于候选疫苗的评估和开发是必不可少的。针对皮肤和相关组织的疫苗接种方法的免疫原性和节省剂量的特性引起了越来越多的关注；对于肠疫苗，皮肤疫苗接种特别受关注。使用皮肤途径时，皮肤疫苗部位反应是最常见且可见的疫苗相关不良事件（AE）。管理严重程度分类的监管指南侧重于功能影响，但不足以表征一系列皮肤反应，也无法比较具有类似局部皮肤AE的途径，剂量和产品。目标我们的小组制定了分级量表，以评估和比较皮肤内疫苗（ID）和经皮免疫（TCI）候选产肠毒素大肠杆菌（ETEC）候选疫苗（基于粘附素的疫苗共与LTR192G一起使用）。我们回顾了表征TCI和ID疫苗接种后局部疫苗部位反应的外观和严重程度的现有方法，并设计了标准化的疫苗部位外观等级量表（VSAGS），用于临床开发新型ETEC候选疫苗，重点关注皮肤的病理生理表现发现。结果已发表报告的可用数据显示，红斑丘疹和瘙痒是与TCI相关的最常见的局部AE。在整个研究中，反应频率的变化显着，TCI疫苗接种方法和产品也是如此。ID疫苗接种通常会导致疫苗部位出现红斑和硬结以及色素沉着的变化。没有公开的方法来表征皮肤病学发现的范围。结论ID和TCI疫苗接种与可预测范围较大的皮肤AE相关。侧重于皮肤变化外观的分级量表可用于比较皮肤AE。标准化的分级量表将有助于记录和比较皮肤AE。结论ID和TCI疫苗接种与很大程度上可预测的皮肤AE相关。侧重于皮肤变化外观的分级量表可用于比较皮肤AE。标准化的分级量表将有助于记录和比较皮肤AE。结论ID和TCI疫苗接种与可预测范围较大的皮肤AE相关。侧重于皮肤变化外观的分级量表可用于比较皮肤AE。标准化的分级量表将有助于记录和比较皮肤AE。