Broad and effective protection against influenza achieved by viral vectored vaccines

季节性流感疫苗被广泛使用，需要每年重新接种，但近年来疫苗的有效性一直很低，特别是在老年人中，他们更有可能经历严重或致命的疾病。在流感大流行的情况下，将需要一种新的疫苗，但在大流行开始后的几个月内不会大量供应。在牛津大学的詹纳研究所，我们一直致力于开发新型流感疫苗，这种疫苗将对季节性和大流行性流感病毒都有效，包括老年人，其中一种疫苗目前正在进行第二阶段临床试验。我们现在正准备测试疫苗的进一步改进。第一种疫苗只包括流感病毒的内部抗原，并增强T细胞对它们的反应。多项研究已经证明，对这些抗原具有高T细胞反应的人可以预防季节性和大流行性流感，我们已经证明，我们可以通过疫苗接种来增强反应，包括老年人。我们现在会在疫苗中加入另一种抗原，以诱导抗神经氨酸酶的抗体。神经氨酸酶是一种在流感病毒表面发现的蛋白质，较已获许可的疫苗的主要抗原血凝素的变异性小。我们亦会测试不同的疫苗接种途径。已获许可的流感疫苗通过肌肉注射给予成年人，并且已知可增加血液中的流感血凝素抗体。然而，病毒感染呼吸道，并且也可以通过将疫苗递送到呼吸道来提高保护。新疫苗将在已经接触过流感病毒的猪身上进行测试，以模拟人类接种疫苗的效果。我们将研究对内部抗原和神经氨酸酶的免疫应答的诱导，以及肌内、上呼吸道或下呼吸道免疫接种后疫苗效力的差异。表达内部抗原的病毒载体流感疫苗已在人体中进行了测试，并显示出安全性，并显着增强T细胞应答。添加另外的抗原和改变疫苗施用途径可能证明在提高疫苗效力方面是非常有益的。

Seasonal influenza vaccines are widely used, requiring annual revaccination, but vaccine effectiveness has been low in recent years, especially in older adults who are more likely to experience severe or fatal disease. In the event of an influenza pandemic, a new vaccine will be required, but will not become available in significant quantities until several months after the pandemic starts. At the Jenner Institute at Oxford University we have been working on the development of novel influenza vaccines that will be effective against both seasonal and pandemic influenza viruses, including in older adults, and one of the vaccines is now in a phase II clinical trial. We are now preparing to test further improvements to the vaccine.The first version of the vaccine includes only internal antigens of the influenza virus and boosts T cell responses to them. Multiple studies have demonstrated protection against both seasonal and pandemic influenza in people who have high T cell responses to these antigens, and we have demonstrated that we can boost responses, including in older adults, by vaccination. We will now include a further antigen into the vaccines, to induce antibodies against neuraminidase, which is a protein found on the surface of the influenza virus and is less variable that haemagglutinin which is the major antigen in licensed vaccines.We will also test different routes of vaccine administration. Licensed influenza vaccines are given to adults by intramuscular injection, and are known to increase antibodies to influenza haemagglutinin in the blood. However the virus infects the respiratory tract, and it may be possible to improve protection by delivering the vaccines to the respiratory tract also. The new vaccines will be tested in pigs which have already been exposed to influenza virus, to mimic the effect of vaccinating humans. We will study the induction of immune responses to both the internal antigens and neuraminidase, as well as testing for differences in vaccine efficacy after intramuscular, upper respiratory tract or lower respiratory tract immunisation. Viral vectored influenza vaccines expressing internal antigens have been tested in humans and shown to be safe, and to significantly boost T cell responses. Adding a further antigen and changing the route of vaccine administration may prove highly beneficial in improving vaccine efficacy.