Clinical assessment of a novel simian adenovirus-vectored influenza vaccine designed to induce broadly protective immunity

旨在诱导广泛保护性免疫的新型猿猴腺病毒载体流感疫苗的临床评估

• 批准号: MR/K015419/1
• 负责人: Sarah Gilbert
• 金额: $ 101.12万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2012
• 资助国家: 英国
• 起止时间: 2012 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FK015419%2F1
• 关键词: Clinical; assessment; novel; simian; adenovirus

The influenza vaccines that are used at present have a number of disadvantages. The vaccines have to be reformulated every year to keep up with changes in the viruses that are circulating, and people have to be revaccinated every year. About one year in 20, the virus that is circulating changes after the vaccine formulation for that year has been decided, and then the vaccine does not work well. At best the trivalent inactivated vaccine (TIV) has an efficacy of 60 % in adults aged under 65 years, and lower than that in older people who are the main group targeted for vaccination. At the Jenner Institute we have tested a new type of influenza vaccine using a live virus vaccine, similar to the smallpox vaccine, which has been attenuated to prevent it from causing disease and make it very safe to use. Our first clinical trials with this new vaccine MVA-NP+M1 showed that it was very effective at boosting T cell immune responses to influenza, and that in a small study, fewer vaccinated than non-vaccinated volunteers who were then exposed to influenza virus developed symptoms of influenza infection. Importantly, the vaccine was very immunogenic in older volunteers, which is not the case with TIV.We now wish to conduct clinical trials with a different viral vectored influenza vaccine, this one based on an attenuated adenovirus, since in clinical trials of vaccines against other diseases this type of vaccine was even more immunogenic and the immune responses lasted for longer after vaccination.The first ever clinical trials of this new vaccine, ChAdOx1 NP+M1, have already started, in a small study designed to work out the best dose to use. We are now applying for funding to do two trials with this new vaccine. The first will be in healthy volunteers aged 18 to 50 years. Half of them will receive ChAdOx1 NP+M1, and half will receive MVA-NP+M1, so that we can compare the immunogenicity of the two vaccines. Later, they will all receive a second vaccination with the vaccine that they did not receive the first time, so that we can see the effect of giving first one vaccine and then the other, as this is expected to produce the strongest and most durable response.The second trial will be in volunteers aged over 50 years who will receive a single dose of ChAdOx1 NP+M1 to determine immunogenicity in older people. After these studies have been completed, we will be able to design much larger studies to find out how effective the vaccine is at preventing people from becoming ill with influenza

目前使用的流感疫苗有许多缺点。疫苗必须每年重新配制，以跟上正在传播的病毒的变化，人们也必须每年重新接种疫苗。大约20年的某一年，当年的疫苗配方确定后，正在传播的病毒发生了变化，然后疫苗就发挥不了作用。三价灭活疫苗（TIV）对65岁以下成年人的有效率最多为60%，低于主要接种人群的老年人。在詹纳研究所，我们使用活病毒疫苗测试了一种新型流感疫苗，类似于天花疫苗，该疫苗已被减毒以防止其引起疾病，并且使用起来非常安全。我们对这种新疫苗 MVA-NP+M1 的首次临床试验表明，它在增强 T 细胞对流感的免疫反应方面非常有效，而且在一项小型研究中，接种疫苗的志愿者比未接种疫苗的志愿者在暴露于流感病毒后出现流感感染症状的人数要少。重要的是，该疫苗在老年志愿者中具有很强的免疫原性，而 TIV 则不然。我们现在希望使用另一种病毒载体流感疫苗进行临床试验，这种疫苗基于减毒腺病毒，因为在针对其他疾病的疫苗的临床试验中，这种疫苗的免疫原性更强，并且接种后免疫反应持续时间更长。有史以来的第一次临床试验 这种新疫苗 ChAdOx1 NP+M1 的研究已经开始，一项小型研究旨在找出最佳使用剂量。我们现在正在申请资金来对这种新疫苗进行两项试验。第一个实验对象是 18 至 50 岁的健康志愿者。其中一半会接种ChAdOx1 NP+M1，一半会接种MVA-NP+M1，这样我们就可以比较两种疫苗的免疫原性。之后，他们都将接受第一次没有接种的疫苗的第二次疫苗接种，这样我们就可以看到先接种一种疫苗，然后再接种另一种疫苗的效果，因为这预计会产生最强、最持久的反应。第二次试验将在 50 岁以上的志愿者中进行，他们将接受单剂 ChAdOx1 NP+M1，以确定老年人的免疫原性。这些研究完成后，我们将能够设计更大规模的研究，以了解疫苗在预防人们感染流感方面的效果如何

项目成果

Heterologous Two-Dose Vaccination with Simian Adenovirus and Poxvirus Vectors Elicits Long-Lasting Cellular Immunity to Influenza Virus A in Healthy Adults.

• DOI: 10.1016/j.ebiom.2018.02.011
• 发表时间: 2018-03
• 期刊: EBioMedicine
• 影响因子: 11.1
• 作者: Coughlan L;Sridhar S;Payne R;Edmans M;Milicic A;Venkatraman N;Lugonja B;Clifton L;Qi C;Folegatti PM;Lawrie AM;Roberts R;de Graaf H;Sukhtankar P;Faust SN;Lewis DJM;Lambe T;Hill A;Gilbert SC
• 通讯作者: Gilbert SC

Measuring Cellular Immunity to Influenza: Methods of Detection, Applications and Challenges.

• DOI: 10.3390/vaccines3020293
• 发表时间: 2015-04-14
• 期刊: Vaccines
• 影响因子: 7.8
• 作者: Coughlan L;Lambe T
• 通讯作者: Lambe T