CAP:Evaluation of a Dengue Vaccine in Adults with Preexisting Flavivirus Immunity

CAP：对已有黄病毒免疫力的成人进行登革热疫苗评估

• 批准号: 10927868
• 负责人: Stephen Whitehead
• 金额: $ 1.67万
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10927868
• 关键词: 12 year old; 17 year old; 4 year old; Acceleration; Admixture; Adolescent; Adult; Age; Agreement; Area; Attenuated; Attenuated Vaccines; Biological Assay; COVID-19; Cellular Immunity; Child; Clinical; Clinical Research; Clinical Trials; Controlled Clinical Trials; Databases; Dengue; Dengue Vaccine; Dengue Virus; Dengvaxia; Dose; Double-Blind Method; Enrollment; Evaluation; Flavivirus; Funding; Genetic; Goals; Human; Immune response; Immunity; Individual; Infant; Manuscripts; Medical Research; National Institute of Allergy and Infectious Disease; Phase; Placebo Control; Program Evaluation; Published Comment; Safety; Sampling; Sampling Studies; Serology test; Thailand; Vaccination; Vaccinee; Vaccines; Viremia; Virus; Work; Writing; age group; antibody test; cohort; experience; follow-up; immunogenicity; programs; vaccine candidate

A detailed statement of work was prepared to describe the activities to be carried out by the AFRIMS group in Bangkok, Thailand. An Interagency Agreement (A-AI-12-051-0000-0000) was executed between NIAID and the U.S. Army Medical Research and Materiel Command and became effective on 09-01-2012. This agreement governs the activities between NIAID and AFRIMS and was initially funded by the NIAID Concept Acceleration Program (CAP) and the Division of Clinical research. CAP funding will be used to support this clinical trial, including the required serological assays, viremia assays, and other clinical activities associated with the evaluation of the tetravalent dengue vaccine. The purpose of this project is to evaluate a live attenuated tetravalent DENV vaccine candidate with regard to safety, tolerability, genetic stability, and immunogenicity in humans, and to study the host's immune response to these viruses. Vaccination will occur in an age de-escalation manner, beginning with adults, followed by adolescents, older children, and finally younger children. Six months after primary vaccination, adult subjects will receive a second dose of tetravalent vaccine and will be followed for an additional 6 months. Two different vaccine admixtures, TV003 and TV005 will be studied in adults. Other age cohorts will only receive TV005. The study will enroll 294 subjects in a double-blind, placebo-controlled clinical trial. Adult cohort received dose 1 on Dec 6, 2014 and dose 2 on June 6, 2015. Adolescent cohort (13 - 17 years old) dosed Mar 2015 (3-YR follow-up ended Mar 2018) Older child cohort (5 - 12 years old) dosed Aug 2015 (3-YR follow-up ended Aug 2018) Younger child cohort (1 - 4 years old) dosed Nov 2015 (3-YR follow-up ended Nov 2018) Currently, all subjects have completed the follow-up phase of the study. The follow-up period was initially set for 1 year, but the US FDA has asked that we follow-up individuals for a period of 3 years (based on the Sanofi-Pasteur Dengvaxia experience). This extended follow-up period also delayed the planned unblinding of the study. Since the last vaccinees was enrolled in the study on Nov 7, 2015, the 3-year follow-up period ended in November 2018. During 2019, the safety databases were locked and the study has been unblinded. All remaining study samples were transferred to the US (LVD and WRAIR). Final antibody assays for the year 3 samples were delayed due to COVID-19. Cellular immunity assays are still pending at WRAIR. A manuscript describing the study results (not including the cellular immune responses) has been written and is circulating for final comments. The manuscript will be submitted in September 2023.

准备了一份详细的工作说明，描述 AFRIMS 小组在泰国曼谷开展的活动。 NIAID 与美国陆军医学研究和物资司令部签署了一项机构间协议 (A-AI-12-051-0000-0000)，并于 2012 年 1 月 9 日生效。该协议管辖 NIAID 和 AFRIMS 之间的活动，最初由 NIAID 概念加速计划 (CAP) 和临床研究部门资助。 CAP 资金将用于支持这项临床试验，包括所需的血清学检测、病毒血症检测以及与四价登革热疫苗评估相关的其他临床活动。 该项目的目的是评估四价 DENV 减毒活疫苗候选物的安全性、耐受性、遗传稳定性和免疫原性，并研究宿主对这些病毒的免疫反应。疫苗接种将以年龄递减的方式进行，从成人开始，然后是青少年、年龄较大的儿童，最后是年龄较小的儿童。初次接种疫苗六个月后，成年受试者将接受第二剂四价疫苗，并继续随访 6 个月。两种不同的疫苗混合物 TV003 和 TV005 将在成人中进行研究。其他年龄组将仅接收 TV005。该研究将招募 294 名受试者参加双盲、安慰剂对照临床试验。 成人队列于2014年12月6日接受第1剂，于2015年6月6日接受第2剂。 青少年队列（13 - 17 岁）于 2015 年 3 月给药（3 年随访截至 2018 年 3 月） 年龄较大的儿童队列（5 - 12 岁）于 2015 年 8 月接种（3 年随访于 2018 年 8 月结束） 年龄较小的儿童队列（1 - 4 岁）于 2015 年 11 月注射（3 年随访于 2018 年 11 月结束） 目前，所有受试者均已完成后续阶段的研究。随访期最初设定为 1 年，但美国 FDA 要求我们对个体进行 3 年的随访（基于赛诺菲巴斯德 Dengvaxia 的经验）。 延长的随访期也推迟了研究计划的揭盲时间。 自2015年11月7日最后一批疫苗接种者参加该研究以来，3年随访期于2018年11月结束。 2019 年期间，安全数据库被锁定，研究也已揭盲。 所有剩余的研究样本均被转移到美国（LVD 和 WRAIR）。由于 COVID-19，第 3 年样本的最终抗体检测被推迟。 WRAIR 的细胞免疫测定仍在进行中。 描述研究结果（不包括细胞免疫反应）的手稿已经编写完毕，正在分发以征求最终意见。 手稿将于2023年9月提交。