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全球1.8亿人，占英国人口的0.5%-1%。大多数感染者没有清除体内的病毒，大约20%的人会发展成严重的肝脏疤痕(肝硬变)，可能需要肝移植。人们不能摆脱丙型肝炎的主要原因之一是免疫系统看不到并攻击病毒。目前最好的治疗方法被称为联合疗法。这种治疗有许多副作用，涉及微弱的注射，许多患者不得不接受一年的治疗。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预防感染的疫苗，或者在联合治疗期间给患者注射疫苗，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，非常成功地刺激了健康人的免疫系统，对抗丙型肝炎病毒。这种疫苗是由普通感冒病毒的一部分--腺病毒--制成的，我们已经将一部分丙型肝炎病毒注入了感冒病毒中。腺病毒的作用就像一个载体，传递部分丙型肝炎病毒，并有望启动免疫系统。重要的是，感冒病毒和丙型肝炎病毒的一部分已经被改变，它们不能复制，本身就会引起感染。我们试图通过给志愿者接种第二种不同但相关的腺病毒疫苗来进一步提高免疫反应。然而，我们无法做到这一点，因为第一针的抗体是在接种疫苗后产生的，因此阻止了第二针的工作(交叉反应抗体)。我们现在希望开发一种与腺病毒载体有很大不同的疫苗载体(MVA)，这样就不会发生交叉反应的问题。我们希望在少数健康和感染丙型肝炎病毒的患者中进行测试。通过这样做，我们相信我们将成功地进一步增强免疫反应，从而显著增加预防或治愈丙型肝炎病毒感染的机会。

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.