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

目前使用的流感疫苗有很多缺点。疫苗必须每年重新配方，以跟上正在传播的病毒的变化，人们必须每年重新接种疫苗。大约每20年有一年，在决定了当年的疫苗配方后，正在传播的病毒发生变化，然后疫苗就不能很好地发挥作用。三价灭活疫苗(TIV)在65岁以下的成年人中充其量只有60%的效果，低于作为主要疫苗接种目标的老年人。在Jenner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，天花疫苗已被减毒，以防止其致病，并使其使用非常安全。我们对这种新疫苗MVA-NP+M1进行的第一次临床试验表明，它在增强T细胞对流感的免疫反应方面非常有效，在一项小型研究中，随后接触流感病毒的接种疫苗的志愿者比未接种疫苗的志愿者更少出现流感感染症状。重要的是，这种疫苗在老年志愿者中具有很强的免疫原性，而TIV并非如此。我们现在希望用一种不同的病毒载体流感疫苗进行临床试验，这种疫苗基于减毒的腺病毒，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，免疫反应在接种后持续更长时间。这种新疫苗ChAdOx1 NP+M1的首次临床试验已经开始，这是一项旨在确定最佳剂量的小型研究。我们现在正在申请资金，用这种新疫苗进行两项试验。首先是年龄在18岁到50岁之间的健康志愿者。其中一半接种ChAdOx1 NP+M1，另一半接种MVA-NP+M1，这样我们就可以比较两种疫苗的免疫原性。随后，他们都将接受第二次接种他们没有第一次接种的疫苗，这样我们就可以看到第一次接种一种疫苗，然后再接种另一种疫苗的效果，因为这预计会产生最强烈和最持久的反应。第二次试验将在50岁以上的志愿者身上进行，他们将接受单剂ChAdOx1 NP+M1来确定老年人的免疫原性。在这些研究完成后，我们将能够设计更大的研究，以找出疫苗在预防人们感染流感方面的效果。

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