Phase Ib trial of a simple, multivalent vaccine to prevent Zika and Chikungunya

预防寨卡和基孔肯雅热的简单多价疫苗的 Ib 期试验

• 批准号: 971557
• 金额: $ 441.34万
• 依托单位: UNIVERSITY OF OXFORD
• 依托单位国家: 英国
• 项目类别: Small Business Research Initiative
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=971557
• 关键词: Phase; Ib; trial; simple; multivalent

The aim of this project is to complete a Phase Ib trial of a new bivalent vaccine to induce simultaneous immunity against Zika and Chikungunya, simplifying future vaccination campaigns for countries where both diseases co-circulate in the same regions, and where protection against both diseases is needed. Infection by ZIKV is a major concern worldwide due to the neurologic conditions, such as Guillain-Barré syndrome and a concurrent 20-fold increase in the incidence of microcephaly during the ZIKV outbreak in Brazil between 2014 and 2015 and in Mexico, where microcephaly caused by ZIKV has been confirmed. Aedes mosquitoes transmit Chikungunya virus (CHIKV), ZIKV and Dengue in the same geographical regions. CHIKV produces symptomatic disease in approximately ¾ of infected people, leading in many cases to long-term sequelae in people of all ages. Persistent arthritis cause disability for several years, contributing to poverty as young adults are unable to perform their physical activities required for work. Costs for families and governments are augmented due to the need to administer anti-inflammatory drugs to provide a short-term relief in patients. No vaccine is yet licensed for the prevention of CHIKV or ZIKV infections.The sudden presence of Zika and Chikungunya in the same geographical regions have overwhelmed health systems that were already challenged by Dengue, thus increasing the failure to provide treatment and preventive measures to their populations during the outbreak, while posing new challenges for treatment of both Zika and Chikungunya due to the long-term sequelae of more than 6 years for these diseases. These diseases are transitioning from an epidemic nature towards endemic diseases due to enabling drivers such as poor socioeconomic conditions, climate change and migration. A major breakthrough will be to provide governments with tools to simultaneously fight these highly prevalent arbovirus diseases and a multivalent vaccine able to protect against both Zika and Chikungunya would be an ideal preventive solution. This proposal has five major aims:1. Production of a large GMP batch of ChAdOx1-Zika (A parallel proposal submitted to Innovate UK could support alarge GMP batch of a ChAdOx1-Chikungunya vaccine).2. A Phase Ib trial of the bivalent vaccine in Mexico, in the city of Veracruz, where both diseases are prevalent.3. A study to assess incidence of Zika and Chikungunya in the ZIKV and CHIKV-endemic regions of Veracruz andMichoacan, to inform future Phase IIb efficacy trials in Mexico.4. Capacity development in Veracruz, Mexico to perform clinical trials.5. Reproduction toxicology for the Zika vaccine to support their use in pregnant women. This will consist of an embryo-foetal, pre- and post-natal development studies in the mouse.This proposal is fully aligned with the Officiald Development Assistance (ODA) and focuses on the development of vaccines that are appropriate for use in low- and middle- income countries, such as Mexico where recent outbreaks of Chikungunya and Zika have taken place in 2015 and 2016, respectively, and where arboviral diseases are contributing to poverty.

该项目的目的是完成一种新的双价疫苗的Ib期试验，以诱导对寨卡病毒和基孔肯雅病毒的同时免疫，简化这两种疾病在同一地区共同传播的国家未来的疫苗接种活动，以及需要预防这两种疾病的国家。ZIKV感染是世界范围内的一个主要问题，这是由于神经系统疾病，如吉兰-巴雷综合征，以及2014年至2015年在巴西和墨西哥ZIKV爆发期间小头畸形的发病率同时增加了20倍，其中ZIKV引起的小头畸形已经得到证实。伊蚊在相同的地理区域传播基孔肯雅病毒（CHIKV）、ZIKV和登革热。CHIKV在大约3/4的感染者中产生症状性疾病，在许多情况下导致所有年龄段的人的长期后遗症。持续性关节炎会导致残疾数年，造成贫困，因为年轻人无法进行工作所需的体力活动。家庭和政府的成本增加，因为需要管理抗炎药物，以提供短期缓解患者。寨卡病毒和基孔肯雅热病毒在同一地理区域的突然出现使已经受到登革热挑战的卫生系统不堪重负，从而增加了在疫情期间为其人口提供治疗和预防措施的失败，同时由于这些疾病超过6年的长期后遗症，对寨卡和基孔肯雅的治疗提出了新的挑战。由于社会经济条件差、气候变化和移徙等促成因素，这些疾病正从流行病性质转变为地方病。一项重大突破将是为政府提供同时对抗这些高度流行的虫媒病毒疾病的工具，而能够预防寨卡病毒和基孔肯雅病毒的多价疫苗将是一种理想的预防解决方案。该提案有五个主要目标：1。生产大批量的ChAdOx 1-Zika GMP（提交给Innovate UK的平行提案可以支持大批量的ChAdOx 1-Chikungunya疫苗）。在墨西哥韦拉克鲁斯市进行的二价疫苗的Ib期试验，这两种疾病都很流行。一项评估韦拉克鲁斯州和米却肯州ZIKV和CHIKV流行地区Zika和Chikungunya发病率的研究，为墨西哥未来的IIb期疗效试验提供信息。在墨西哥韦拉克鲁斯州进行临床试验的能力发展。寨卡病毒疫苗的生殖毒理学，以支持其在孕妇中的使用。这将包括对小鼠胚胎-胎儿、产前和产后发育的研究。该提案完全符合联合国开发援助计划署（ODA）的要求，重点是开发适用于低收入和中等收入国家的疫苗，例如墨西哥，该国最近分别在2015年和2016年爆发了基孔肯雅病毒和寨卡病毒。以及虫媒病毒疾病导致贫困的地方。