Correlating gene expression changes and innate immune responses with protective SIV vaccination in cynomolgus macaques

约有3300万艾滋病毒/艾滋病携带者，约2500万人死亡。人们迫切需要一种保护性疫苗，但最近所有的艾滋病毒疫苗试验都失败了。这主要是因为我们并不真正了解好的疫苗是如何起作用的。在猴子身上，唯一可靠有效的疫苗策略是用活的减毒病毒接种。这在人类身上是不可接受的，因为减毒病毒最终可能会使接种疫苗的人生病，他们可能会将其传染给其他人。这项研究旨在找出疫苗病毒对接种疫苗的动物产生了什么作用，使它们对第二次感染具有免疫力。在NIBSC早期工作的基础上，我们提出，疫苗接种刺激了病毒感染的特定细胞中的先天免疫。这意味着被疫苗病毒感染的细胞被刺激产生蛋白质，以保护它们和周围的细胞免受进一步感染。我们将通过测量疫苗接种后数量的变化来确定重要的基因和蛋白质。在一种平行的方法中，我们将准确地测量已知具有抗逆转录病毒特性的特定蛋白质的数量，比较接种疫苗和未接种疫苗的动物。通过这种方式，我们将寻求先天免疫在保护性疫苗接种中的作用。一旦我们确定了疫苗接种后出现的蛋白质，我们将测试它们的抗病毒特性。这项研究的一个重要方面是NIBSC和UCL之间的密切互动，它们赞助在疫苗研究(NIBSC)和分子病毒学和先天免疫(UCL)方面具有丰富经验的中心之间的技术和专业知识转让。

There are around 33 million people living with HIV/AIDS and around 25 million people have died. There is a desperate need for a protective vaccine but all the recent HIV vaccine trials have failed. This is essentially because we don t really understand how good vaccines work. In monkeys, the only vaccine strategy that works reliably is vaccination with live attenuated virus. This is not acceptable in humans because the attenuated virus could eventually make the vaccinated person ill and they may pass it on to others. This study aims to find out what it is that the vaccine virus does to the vaccinated animals, that makes them immune to a second infection. Based on earlier work at NIBSC we propose that vaccination stimulates innate immunity in the specific cells that the virus infects. This means that the cells infected with the vaccine virus are stimulated to make proteins that protect them and surrounding cells from further infection. We will identify the important genes and proteins by measuring change in their amounts after vaccination. In a parallel approach we will accurately measure amounts of specific proteins known to have anti retroviral properties, comparing vaccinated and unvaccinated animals. In this way we will seek a role for innate immunity in protective vaccination. Once we have identified proteins that appear after vaccination, we will test them for antiviral properties. An important aspect of this study is the close interaction between NIBSC and UCL sponsoring the transfer of technologies and expertise between centres with considerable experience in vaccination studies (NIBSC) and molecular virology and innate immunity (UCL).