VACCINE: Velcro vaccines: directing an enhanced immune response

由马链球菌引起的窒息仍然是世界各地最常见的马传染病，冰岛是一个明显的例外。英国每年发生超过600起勒死事件，导致马事件的严重中断，并给英国经济每年价值超过70亿英镑的行业造成损失。所有受感染的马在爆发期间都可能出现疾病的临床体征，其中约2%需要安乐死。大约10%的恢复马成为持续感染。在参加马术比赛或销售期间，未接触过马的健康带菌者动物会脱落马链球菌，这很难避免。因此，安全有效的疫苗的可用性，保护马免于发展窒息，尽管它们暴露于马链球菌，将对世界各地的马福利和马术活动产生深远的影响。然而，欧洲唯一可用的扼杀疫苗，一种名为Equilis StrepE的活细菌疫苗，只能在很短的时间内（3个月）为马提供保护。我们已经修改了最近发现的一种名为SzeQ的超抗原，它通常会误导免疫反应，因此它可以用来加强对疫苗接种的免疫反应。在这个项目中，我们建议将修饰后的SzeQ与来自马链球菌的蛋白质融合，它可以直接使用，也可以用作原型勒死疫苗表面的粘性涂层。这种被毛将作为一种“尼龙搭扣”，附着在免疫细胞上，提高免疫反应的强度和持续时间。我们将首先在实验室中生产和纯化尼龙搭扣蛋白，并测量其活性和诱导小马持久免疫反应的能力。然后，我们将其附着在一个控制菌株的马链球菌表面，并测量其粘附免疫细胞的能力。最后，我们将在扼杀疫苗原型的表面上生产Velcro蛋白，并确定它是否能提高小马接种疫苗后产生的免疫应答的强度和持续时间，以及这些应答在实验室中杀死马链球菌的能力。该项目有可能解决开发安全有效疫苗的重大问题，这些疫苗可以预防这种高度流行和马的重要疾病此外，Velcro蛋白或其变体的偶联还可以增强一系列其他疫苗保护猪、牛、羊和人的有效性。

Strangles, caused by Streptococcus equi remains the most frequently identified infectious disease of horses around the World, with the notable exception of Iceland. Over 600 outbreaks of strangles occur in the UK each year leading to significant disruption of equine events and cost to an industry worth over £7 billion per annum to the UK economy. All infected horses may suffer clinical signs of disease during the course of an outbreak, with approximately 2% requiring euthanasia. Approximately 10% of recovered horses become persistently infected. The exposure of naïve horses to Streptococcus equi that is shed from healthy carrier animals during participation in equestrian events or sales is difficult, if not impossible, to avoid. Therefore, the availability of a safe and effective vaccine that protects horses from developing strangles despite their being exposed to Streptococcus equi would have far-reaching benefits for equine welfare and equestrian activities throughout the World. However, the only available strangles vaccine in Europe, a live bacterial vaccine known as Equilis StrepE, provides protection to horses for only a short period of time (3 months). We have modified a recently identified superantigen, named SzeQ, which normally misdirects the immune response, so that it can instead be used to strengthen the immune response to vaccination. In this project we propose to fuse the modified SzeQ to proteins from Streptococcus equi, which can either be used directly, or be employed as a sticky coat on the surface of a prototype strangles vaccine. This coat will act as a type of 'Velcro', which attaches to immune cells, improving the strength and duration of the immune response.We will first produce and purify the Velcro protein in the laboratory and measure its activity and ability to induce a long-lasting immune response in ponies. Then we will attach it to the surface of a control strain of Streptococcus equi and measure its ability to stick to immune cells. Finally, we will produce the Velcro protein on the surface of a prototype strangles vaccine and determine if it improves the strength and duration of the immune responses produced following the vaccination of ponies and the ability of these responses to kill Streptococcus equi in the laboratory.This project has the potential to solve a significant problem in the development of safe and effective vaccines that protect against this highly prevalent and important disease of horses. Furthermore, coupling of the Velcro protein, or versions thereof, could also enhance the effectiveness of an array of other vaccines to protect pigs, cattle, sheep and man.