Translational Use of Intradermal Needle-free Injector to facilitate and optimize global fractional dose HPV vaccine administration

项目总结 宫颈癌是女性的第四大常见癌症，导致约57万新病例 2018年死亡人数超过30万人，其中大部分发生在低收入和中等收入国家(Bray， 2018年)。在印度尼西亚，宫颈癌是女性中第二常见的癌症类型， 32,000个新病例和18,000个死亡(全球癌症观察站，2019年)。已经证明，人类 人乳头瘤病毒(HPV)感染是宫颈癌的主要致病因素(Bosch，2002)。2017年， 世卫组织发布了一份HPV疫苗立场文件，指出HPV疫苗应列入国家 免疫方案的主要目标人群是9-14岁的女孩，在性行为之前 积极(世界卫生组织，2017年)。疫苗接种代表着最具成本效益和效率的 预防由人乳头瘤病毒引起的宫颈癌的方法。目前，HPV疫苗已经有了 已在全球近100个国家(52%)推广，主要是在中上收入和高收入国家 国家。然而，它在负担最重的国家(低收入和中等收入)的获取仍然滞后。 此外，全球卫生组织之前收集的数据显示，这一数字持续较低 HPV疫苗的合规率，部分原因是针头恐惧症。据预测，这一期将 除非引入新的疫苗接种战略，否则将持续存在。 在这个直接到第二阶段的提案中，我们将探索减少剂量的可行性和潜在的好处 HPV疫苗的皮内策略。在这项更大的研究中，我们将评估剂量和路线 给药以确定患者和照顾者的免疫原性、反应性和水平 每个人都能接受。在资源最少的环境中，使用无针注射进行分娩的好处 预计将包括节省剂量，提高依从性，以及预防针刺伤 和疾病传播。这些研究的结果将提供临床数据来回答主要 当前HPV疫苗计划存在的问题：1)疫苗剂量的可获得性；2)成本；3) 可接受性和合规性。这些数据将是促进未来政策讨论和全球 关于在印度尼西亚和其他发展中国家管理FiHPV疫苗的卫生战略 国家。紧随其后的下一步将包括计划在多个地区开展更大规模的推广活动 在印度尼西亚，特别是在更偏远的地区，疫苗接种依从性一直处于历史低位。 最终，这些研究将被用作提高人们对PharmaJet Tropis针头的认识的工具- 免费注射系统作为FHPV管理的一种方法，可能有助于在全国和世界范围内 世卫组织和卫生部建议的疫苗依从性和可接受性 健康。

PROJECT SUMMARY Cervical cancer is the fourth most common cancer in women, contributing to about 570,000 new cases and more than 300,000 deaths in 2018, most of it occurs in the low- and middle-income countries (Bray, 2018). In Indonesia, cervical cancer is the second most prevalent type of cancer among women, with 32,000 new cases and 18,000 deaths (Global Cancer Observatory, 2019). It has been shown that human papillomavirus (HPV) infection is the major causative agent of cervical cancer (Bosch, 2002). In 2017, WHO released an HPV vaccine position paper that stated HPV vaccines should be included in national immunization programs with its primary target population is 9-14 year old girls, prior to becoming sexually active (World Health Organization, 2017). Vaccination represents the most cost-effective and efficient way for the prevention of cervical cancer caused by human papillomavirus. Currently, HPV vaccine has been introduced in nearly 100 countries globally (52%), mainly in the upper-middle- and high-income countries. However, its access in the highest burden countries (low and middle income) remains lagging. Furthermore, previous data collected by global health organizations have shown continued low compliance rates for HPV vaccines, partly attributable to needle-phobia. It is predicted that this issue will persist unless a new strategy for vaccination is introduced. In this direct to Phase II proposal, we will explore the feasibility and potential benefits of a reduced dose intradermal strategy for HPV vaccines. In this larger study, we will evaluate doses and routes of administration to determine the immunogenicity, reactogenicity, and levels of patient and caregiver acceptance for each. In settings with minimal resources, the benefits of delivery with needle-free injection are predicted to include dose savings, increased compliance, and the prevention of needle-stick injuries and disease transmission. The results from these studies will provide clinical data to answer the main problems with the current HPV vaccine schedule: 1) availability of vaccine doses; 2) cost; and 3) acceptability & compliance. This data will be a first step to facilitate future policy discussions and global health strategies regarding administration of fiHPV vaccines across Indonesia and other developing countries. The immediate next steps will include planning a larger roll-out campaign across multiple areas of Indonesia, notably in further remote areas where vaccination compliance has been historically low. Ultimately, these studies will be used as a tool to increase awareness of the PharmaJet Tropis Needle- free injection system as a method for fiHPV administration that may aid in country-wide and worldwide vaccine compliance and acceptability to schedules as recommended by the WHO and Ministries of Health.