MICA: Developmental Clinical Studies-a novel vaccine candidate MVA-NS for use in a prime boost schedule in HCV infection.

丙型肝炎病毒目前感染了全球1.8亿人，占英国人口的0.5-1%。大多数被感染的人没有从体内清除病毒，大约20%的人会出现严重的肝瘢痕（肝硬化），可能需要肝移植。人们无法摆脱丙型肝炎的主要原因之一是免疫系统无法看到并攻击病毒。目前最好的治疗方法称为联合治疗。这种治疗有许多副作用，需要弱注射，许多患者必须服用一年。在这种治疗结束时，不到一半的患者摆脱了病毒。我们的目标是开发一种疫苗，可以预防感染，或者在联合治疗期间给予患者，以便更多的患者摆脱病毒。 到目前为止，我们已经开发出一种疫苗，非常成功地刺激健康人的免疫系统对抗HCV病毒。这种疫苗是由普通感冒病毒的一部分制成的--一种腺病毒--我们把丙型肝炎病毒的一部分放进了感冒病毒中。腺病毒就像一个载体，运送丙型肝炎病毒的一部分，并有望打开免疫系统。重要的是，感冒病毒和丙型肝炎病毒的一部分已经改变，它们不能复制，本身会引起感染。我们试图通过给志愿者注射第二种不同但相关的腺病毒疫苗来进一步增强免疫反应。然而，我们无法实现这一点，因为第一次注射的抗体在接种疫苗后产生，因此阻止了第二次注射（交叉反应抗体）。我们现在希望开发一种与腺病毒载体完全不同的疫苗载体（MVA），以便不会发生交叉反应性的问题。我们希望在少数健康和HCV感染患者中进行测试。通过这样做，我们相信我们将成功地进一步增强免疫反应，从而显着增加预防或治愈HCV感染的机会。

Hepatitis C virus currently infects 180 million people world-wide and 0.5-1% of the population in the United Kingdom. The majority of people that become infected do not clear the virus from the body and approximately 20% of people will develop severe liver scarring (cirrhosis) and may require liver transplantation. One of the main reasons why people do not get rid of hepatitis C is that the immune system does not see and attack the virus. The current best treatment is called combination therapy. This treatment has many side effects, involves weakly injections and has to be given for a year in many patients. At the end of this treatment less than half of patients get rid of the virus. Our aim is to develop a vaccine that will prevent infection or that is given to patients during combination therapy so that more patients will get rid of the virus. To date we have developed a vaccine that very successfully stimulates the immune system of healthy people against the HCV virus. This vaccine is made from a part of the common cold virus-an adenovirus-and we have put a part of the hepatitis C virus into the cold virus. The adenovirus acts like a carrier to deliver the part of the hepatitis C virus and hopefully turn on the immune system. Importantly, the cold virus and the part of the hepatitis C virus have been altered to that they cannot replicate and themselves cause an infection. We have tried to increase the immune response further, by giving a second different but related adenoviral vaccine to the volunteers. However, we were unable to achieve this as antibodies to the first injection developed after vaccination and so prevented the second one from working (cross-reactive antibodies). We now wish to develop a vaccine vector (MVA) that is quite different from adenoviral vectors so that the problem of the cross reactivity will not occur. We wish to test this in a small number of healthy and HCV infected patients. In doing so, we believe we will successfully boost the immune response further, and so significantly increase the chances of preventing or curing HCV infection.