A non-inferiority trial to assess the safety and immunogenicity of yellow fever vaccine dose sparing strategies for campaign and programmatic use

一项非劣效性试验，旨在评估用于运动和规划使用的黄热病疫苗剂量节约策略的安全性和免疫原性

• 批准号: MC_EX_MR/R006148/1
• 负责人: Ed Clarke
• 金额: $ 140.08万
• 依托单位: MRC Unit the Gambia
• 依托单位国家: 英国
• 项目类别: Research Grant
• 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=MC_EX_MR%2FR006148%2F1
• 关键词: non; inferiority; trial; assess; safety

Yellow fever is a viral infection which is transmitted from person to person by mosquitos. The virus is found in a total of 44 countries across sub-Saharan Africa and South America and most recent estimates suggest that it now causes more than one-million infections each year including 180 000 severe cases and 78 000 deaths in Africa alone. These infections continue to occur despite the availability of a safe and highly effective vaccine which confers lifelong protection against disease after only a single injection. In 2016, the worst epidemic (disease outbreak) of yellow fever in 30 years occurred in Central Africa. Cases due to international travel, also occurred in China sparking fears of uncontrolled disease spread in Asia. The epidemic occurred on the background of progressive increases in yellow fever disease over the past two decades and drove the publication of a new 'Global Strategy to Eliminate Yellow Fever Epidemics' by the World Health Organisation (WHO) in late 2016. This document highlighted the emerging global threat posed by the yellow fever and the major role played by shortages of the yellow fever vaccine in the current disease resurgence. Nearly half of the 34 countries which have introduced the vaccine into their routine immunization schedule for infants ran out of vaccine between 2013 and 2015 with many countries receiving only 50% of the number of doses of the vaccine they needed. These shortages got worse during the recent epidemic when, faced with the possibility of running out of vaccine completely, the WHO took the decision to recommend that 'fractional' doses of the vaccine should be used in the emergency vaccination campaigns being used to control the outbreak. In this way, one fifth (0.1mL) of the normal dose (0.5mL) is given to each person meaning that five times as many people can be vaccinated. There are no studies to see how good fractional doses of the yellow fever vaccine are in babies and children and no studies of have tested fractional doses of the vaccine in sub-Saharan Africa. This is why this study is important. The mains questions we want to ask in 9 to 12 month old Gambian infants are:1. Does giving a fractional dose of a yellow fever vaccine to an infant given them as much protection from yellow fever infection as giving them a full dose of the vaccine? 2. Is there a difference in the amount of protection from yellow fever generated when a fractional dose is given subcutaneously (under the skin - the normal way yellow fever vaccines are given) or intradermally (into the skin)3. Is there any difference in the safety of a fractional dose of the vaccine depending on whether it is given subcutaneously or intradermally? The results of the study will give the WHO expert committee on vaccination policy important information. It will help them to decide if fractional rather than full doses of the yellow fever vaccine can be recommended for future emergency vaccination campaigns including infants and children. It will also help them to decide if fractional rather than full doses can be given to infants as part of their routine scheduled vaccinations or in preventative campaigns. It is hoped that the results of the study will help to stop yellow fever epidemics across sub-Saharan Africa in the future.

黄热病是一种病毒感染，通过蚊子在人与人之间传播。该病毒在撒哈拉以南非洲和南美洲的44个国家被发现，最近的估计表明，它现在每年造成超过100万例感染，其中包括18万例严重病例和7.8万例死亡。尽管有一种安全和高效的疫苗，只需注射一次就能终身预防疾病，但这些感染仍在继续发生。2016年，中非发生了30年来最严重的黄热病疫情（疾病暴发）。由于国际旅行而引起的病例也发生在中国，引发了对亚洲疾病不受控制传播的担忧。在过去20年中，黄热病疫情持续上升，世界卫生组织（世卫组织）于2016年底发布了新的“消除黄热病疫情全球战略”。该文件强调了黄热病构成的新的全球威胁以及黄热病疫苗短缺在当前疾病死灰复燃中发挥的主要作用。2013年至2015年，在将该疫苗纳入婴儿常规免疫计划的34个国家中，近一半的国家用完了疫苗，许多国家只获得了所需疫苗剂量的50%。在最近的疫情期间，这些短缺变得更加严重，当时，面对疫苗完全耗尽的可能性，世界卫生组织决定建议在用于控制疫情的紧急疫苗接种运动中使用“部分”剂量的疫苗。通过这种方式，每个人可以接种正常剂量（0.5mL）的五分之一（0.1mL），这意味着可以接种五倍的人。目前还没有研究表明黄热病疫苗的分次剂量对婴儿和儿童有多好，也没有研究在撒哈拉以南非洲测试过疫苗的分次剂量。这就是为什么这项研究很重要。我们想问9至12个月大的冈比亚婴儿的主要问题是：1。给婴儿接种部分剂量的黄热病疫苗是否与给他们接种全剂量的疫苗一样能保护他们免受黄热病感染？2.当分次剂量皮下注射（皮肤下-黄热病疫苗的正常接种方式）或皮内注射（皮肤内）时，对黄热病的保护作用是否有差异3.分次接种疫苗的安全性是否因皮下或皮内接种而存在差异？研究结果将为世卫组织疫苗接种政策专家委员会提供重要信息。这将有助于他们决定是否可以推荐部分而不是完整剂量的黄热病疫苗用于未来的紧急疫苗接种活动，包括婴儿和儿童。它还将帮助他们决定是否可以将部分剂量而不是全部剂量给予婴儿作为其常规计划接种疫苗或预防活动的一部分。希望这项研究的结果将有助于在未来阻止撒哈拉以南非洲地区的黄热病流行。

项目成果

Th17 responses to pneumococcus in blood and adenoidal cells in children.

Th17 对儿童血液和腺样细胞中肺炎球菌的反应。

• DOI: 10.1111/cei.13225
• 发表时间: 2019
• 期刊: Clinical and experimental immunology
• 影响因子: 4.6
• 作者: Oliver E

The Fourth International Neonatal and Maternal Immunization Symposium (INMIS 2017): Toward Integrating Maternal and Infant Immunization Programs.

第四届国际新生儿和母体免疫研讨会（INMIS 2017）：旨在整合母亲和婴儿免疫计划。

• DOI: 10.1128/msphere.00221-18
• 发表时间: 2018-11-07
• 期刊: mSphere
• 影响因子: 4.8
• 作者: Munoz FM;Van Damme P;Dinleyici E;Clarke E;Kampmann B;Heath PT;Levy O;Leuridan E;Cutland C;Sobanjo-Ter Meulen A;Marchant A
• 通讯作者: Marchant A