What Constitutes a Protective CTL Response in HIV-1 Infection?

什么构成了良好的免疫反应？为什么有些艾滋病毒感染者几个月就患上艾滋病，而另一些人却健康几十年？你的基因如何影响你感染的结果？这些都是我们试图回答的基本问题。艾滋病毒流行病的规模令人震惊。在撒哈拉以南非洲的一些地区，每3个成年人中就有1人受到感染。现在迫切需要一种廉价有效的疫苗。设计艾滋病毒疫苗的第一步是了解它应该诱导的免疫类型，即究竟什么是良好的免疫反应？因为HIV会破坏免疫细胞，所以回答这个问题很复杂。因此，我们无法判断与良好的病毒控制相关的免疫反应属性是低水平病毒的原因还是结果。这意味着许多研究免疫反应的传统方法是多余的。关于是什么决定了人类免疫反应的效力，一个线索在于观察到有些人天生比其他人更好地控制艾滋病毒感染，这在一定程度上与人的基因构成有关。这个项目的目的是通过理解为什么一些基因比其他基因产生更好的免疫控制来理解什么是良好的免疫反应。这项研究将通过对现有艾滋病毒感染患者数据库进行新颖的数学分析来进行。我们的研究结果将有助于我们理解什么是良好的免疫反应。这可能对人类健康和艾滋病毒疫苗的开发产生直接影响。更一般地说，艾滋病、疟疾和结核病这三种世界上最具破坏性的疾病的严重程度部分取决于宿主的遗传。我们希望我们的研究产生的方法和见解将适用于所有这些情况。

What constitutes a good immune response? Why do some HIV-infected people develop AIDS in months whilst others remain healthy for decades? How do your genes affect your outcome of infection? These are the fundamental questions that we are trying to answer. The size of the HIV pandemic is staggering. In some areas of sub-Saharan Africa 1 in every 3 adults are infected. A cheap effective vaccine is desperately needed. The first step in designing an HIV vaccine is understanding the type of immunity that it should induce, i.e. what exactly is a good immune response? Answering this question is complicated by the fact that HIV destroys immune cells. Consequently we cannot tell if immune response attributes associated with good viral control are a cause or an effect of low levels of virus. This means that many traditional methods of investigating the immune response are redundant. A clue as to what determines the efficacy of the human immune response lies in the observation that some people naturally control HIV infection much better than others and that this is, in part, related to the person’s genetic makeup. The aim of this project is to understand what a good immune response is by understanding why some genes result in better immune control than others. The research will be conducted by a novel mathematical analysis of existing HIV-infected patient databases. Our results will contribute to our understanding of what constitutes a good immune response. This could have direct implications for human health and HIV vaccine development. More generally, severity of illness for all 3 of the world’s most devastating diseases: AIDS, malaria and TB is partially determined by host genetics. We hope that the methods and insights our research generates will be applicable in all of these cases.