Developmental Clinical Study - UK HVC 003 DMP Phase I Prime-Boost-ReBoost HIV vaccine trial

与艾滋病毒相关的全球健康负担继续增加，2009年估计有3300万人感染艾滋病毒，270万新感染病例。在没有治愈方法的情况下，有效的疫苗将是预防新的艾滋病毒感染的最可持续的方法。我们建议充分利用我们从以前的一系列疫苗试验中学到的知识，设计和测试一种艾滋病毒疫苗策略，我们认为这种策略将引发比迄今为止观察到的更好的免疫反应，并有可能导致确定成功的疫苗和疫苗策略。该提案汇集了科学专业知识和一系列疫苗产品，这些疫苗产品是针对主要存在于南部和东非、印度和尼泊尔的一种常见艾滋病毒设计的，这种病毒造成了世界上最严重的艾滋病毒流行，并导致了大约一半的感染。这项研究将与英国艾滋病毒疫苗联盟（UK HVC）合作进行，该联盟的任务是产生一系列含有类似艾滋病毒抗原的候选疫苗，以便能够实现直接比较，以最迅速地了解最具免疫原性的人类免疫策略。英国HVC 001DMP试验的设计基于一种免疫方案，类似于唯一一项证明部分有效的艾滋病毒疫苗试验（RV144，显示泰国艾滋病毒感染减少31%）所使用的免疫方案。该研究将探索这种新型HIV候选疫苗组合的安全性和免疫原性，并将正式探索使用英国HVC提供的不同候选疫苗的初始、增强和再增强策略的免疫学影响。它还将探索将候选疫苗组合在一起的有效性，以及最小化对疫苗可行性至关重要的治疗方案长度的额外优势。一种成功和安全的艾滋病毒疫苗将对一般人群和高危人群产生相当大的益处。它有可能在15年的时间里预防7000多万例感染。如果试验确定了有希望的疫苗结构或策略，该研究将支持下一个临床研究的设计，并提供一个机会，为艾滋病毒预防若干领域的决策和政策制定提供信息和支持。

The global health burden associated with HIV continues to grow with 33 million people estimated to be living with HIV in 2009 and 2.7 million new infections. In absence of a cure, an effective vaccine would be the most sustainable way to prevent new HIV infections. We propose to make the most of what we have learned from a series of previous vaccine trials to design and test an HIV vaccine strategy which we believe will trigger a better immune response than those observed so far and potentially lead to the identification of a successful vaccine and vaccine strategy.The proposal brings together the scientific expertise and a range of vaccine products that are designed around a common HIV virus found predominantly in Southern and East Africa, India and Nepal and which has caused the world s worst HIV epidemics and is responsible for around half of all infections. The study will be conducted in collaboration with the UK HIV Vaccines Consortium (UK HVC) whose mission is to generate a series of candidate vaccines containing similar HIV antigens, such that direct comparison can be achieved to understand most rapidly the most immunogenic strategy for immunization in man.The design of the UK HVC 001DMP trial is based on an immunisation regimen similar to that used in the only HIV vaccine trial to demonstrate partial efficacy (RV144, which showed a 31% reduction in HIV infection in Thailand). The study will explore both the safety and immunogenicity of this novel combination of HIV vaccine candidates and will formally explore the immunological impact of a prime, boost and re-boost strategy using different vaccine candidates provided by the UK HVC. It will also explore the effectiveness of combining vaccines candidate together with the added advantage of minimising the length of the regimen seen as crucial to vaccine feasibility.A successful and safe HIV vaccine would have considerable benefits across the general populations and high risk groups. It could have the potential to prevent over 70 million infections over the course of 15 years. Should the trial identify promising vaccine constructs or strategies, the research would support the design of the next clinical studies and provide an opportunity to inform and support decisions and policy making in several areas of HIV prevention.