MICA: Ad4HIV, A Phase I Trial Investigating Ad4, MVA and Protein Immunisation Strategies to Maximise Protective Antibody Responses to HIV-1 Envelope

与艾滋病毒有关的全球健康负担继续增加，2013年估计有3500万艾滋病毒携带者和230万新感染者。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式。我们建议最大限度地利用我们从以前的一系列疫苗试验中学到的东西来设计和测试艾滋病毒疫苗策略，我们相信这种策略将引发比迄今观察到的更好的免疫反应，并可能导致确定成功的疫苗和疫苗策略。该方案汇集了科学、临床和技术专业知识以及一系列疫苗产品，这些产品是围绕一种常见的艾滋病毒设计的，这种病毒主要在南部和东非、印度和尼泊尔发现，这种病毒导致了世界上最严重的艾滋病毒流行，约占所有感染病例的一半。这项研究将与工业合作伙伴PaxVax和英国艾滋病毒疫苗联盟(UK HVC)合作进行。PaxVax是一家完全整合的疫苗公司，其创始人致力于以对社会负责的方式开发创新疫苗技术并将其商业化，以产生全球影响。英国HVC是由Wellcome Trust资助的一项计划，其任务是生产一系列含有类似HIV抗原的候选疫苗，以便可以实现直接比较，以最快地了解人类最具免疫原性的免疫策略。Ad4HIV试验的设计基于一种免疫方案，该方案类似于唯一一项证明部分疗效的艾滋病毒疫苗试验(RV144，该试验显示泰国的感染率最初减少了60%，降至31%)，并建立在现有MRC DC资助的研究(英国HVC发言003)的基础上，它将与之相媲美。Ad4HIV研究将探索一种新的候选艾滋病毒疫苗组合的安全性和免疫原性，并将正式探索一种更短、更简单的Prime-Boost策略的免疫学影响，该策略使用由英国HVC提供的候选疫苗，旨在诱导对感染艾滋病毒的可持续水平的保护超过60%。它还将探索不同加强策略的有效性，以及简化被视为对疫苗可行性至关重要的方案的额外优势。一种成功和安全的艾滋病毒疫苗将对普通人群和高危人群产生相当大的好处。它有可能在15年内预防7000多万人感染。如果试验确定了有前景的疫苗结构或策略，研究将支持下一步临床研究的设计，并提供机会，为艾滋病毒预防的几个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 35 million people estimated to be living with HIV in 2013 and 2.3 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, clinical, and technical 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 an industrial partner, PaxVax, and the UK HIV Vaccines Consortium (UK HVC). PaxVax is a fully integrated vaccine company, whose founders set out to develop and commercialize an innovative vaccine technology in a socially responsible manner for global impact. The UK HVC is a Wellcome Trust funded programme 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 Ad4HIV trial is based on an immunisation regimen similar to that used in the only HIV vaccine trial to demonstrate partial efficacy (RV144, which showed an initial 60% reduction in infection rapidly waning to 31% in Thailand) and which builds on an existing MRC DCS funded study (UK HVC Spoke 003) to which it will be comparable. The Ad4HIV study will explore both the safety and immunogenicity of a novel combination of HIV vaccine candidates and will formally explore the immunological impact of a shorter and simpler prime-boost strategy using vaccine candidates provided by the UK HVC and designed to induce sustainable levels of protection form HIV acquisition of more than 60%. It will also explore the effectiveness of different boosting strategies with the added advantage of simplifying 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.