Nomura Yumiko, Noda Kiyohito, Oohashi Yuusuke, Okuda Shin, Matsumoto Jun, Nakano Takashi, Tsuchida Nao, Ishii Ken J, Hayashi Kunihiko, Iiyama Tatsuo, Onodera Hiroshi, Ishii Koji, Shikano Mayumi, Okabe Nobuhiko
Graduate School of Pharmaceutical Sciences, Tokyo University of Science, 162-8601, Tokyo, Japan; Ministry of Health, Labour and Welfare, 100-8916, Tokyo, Japan.
Faculty of Pharmaceutical Sciences, Tokyo University of Science, 162-8601, Tokyo, Japan.
Vaccine. 2022 Oct 12;40(43):6295-6304. doi: 10.1016/j.vaccine.2022.09.036. Epub 2022 Sep 24.
The development of vaccines against infectious diseases requires a different approach from that of therapeutics, because vaccines are inoculated into healthy individuals and have a preventive effect by activating the immunity of the inoculated human. In Japan, "The Guideline for Clinical Trials of Vaccines for the Prevention of Infectious Diseases" was published in 2010 before changes occurred in the vaccine development environment in Japan, such as the introductions of foreign vaccines and simultaneous global development. This study aimed to identify current challenges in vaccine development through a questionnaire-based survey of pharmaceutical companies in Japan and by comparing the domestic and international guidelines and surveying review reports of 35 vaccines approved in Japan between April 2010 and December 2020. Identified challenges included the requirement for protective efficacy trials, efficacy evaluation of combination vaccines, development of multiregional and foreign clinical trials, and immunization of older adults and immunocompromised patients. We propose that new vaccines against infectious diseases should be evaluated for the protective efficacy, preferably through multiregional clinical trials. Additionally, differences in the incidence of infectious diseases or in epidemic virus strains between regions may affect the trials, when multiregional clinical trials are conducted, but immunogenicity-based studies can be conducted if a correlation between protective efficacy and immunogenicity has been established. We suggest that licensed combination vaccines can be used as comparators when an antigen is added to a licensed combination vaccine. We also proposed that the efficacy of a vaccine in non-major subjects, such as older adults or immunocompromised patients could be evaluated by comparing immunogenicity in major subjects with the confirmed protective effects of the vaccine. It is expected that these revisions will lead to the rapid advancement of vaccine development, which should contribute to the improvement of public health.
针对传染病的疫苗研发需要一种与治疗药物不同的方法，因为疫苗是接种到健康个体体内，并通过激活接种者的免疫力来发挥预防作用。在日本，《预防传染病疫苗临床试验指南》于2010年发布，当时日本的疫苗研发环境尚未发生变化，比如外国疫苗的引入以及同步全球研发。本研究旨在通过对日本制药公司进行问卷调查，并比较国内和国际指南以及调查2010年4月至2020年12月期间在日本获批的35种疫苗的审评报告，来确定疫苗研发当前面临的挑战。所确定的挑战包括保护性效力试验的要求、联合疫苗的效力评估、多区域和国外临床试验的开展，以及老年人和免疫功能低下患者的免疫接种。我们建议，针对传染病的新型疫苗应评估其保护性效力，最好通过多区域临床试验进行评估。此外，在进行多区域临床试验时，不同地区传染病发病率或流行病毒株的差异可能会影响试验，但如果已经确定了保护性效力与免疫原性之间的相关性，则可以开展基于免疫原性的研究。我们建议，当向已获许可的联合疫苗中添加抗原时，已获许可的联合疫苗可作为对照。我们还提议，可以通过比较主要受试者的免疫原性与疫苗已确认的保护效果，来评估疫苗在老年人或免疫功能低下患者等非主要受试者中的效力。预计这些修订将推动疫苗研发的快速进展，这将有助于改善公众健康。
