Human infection challenge vaccine (HIC-vac) network

尽管疫苗每年拯救了全球数百万人的生命，但仍有许多传染病导致大量人死亡，而接种疫苗仍无法预防这些疾病。在中低收入国家尤其如此，那里甚至无法获得基本的医院治疗，唯一现实的选择是通过寻找新的、经济上可行的疫苗来预防传染病。几百年来，英国在通过人体实验取得原创性科学发现方面一直处于世界领先地位。尽管感染病原体的人显然存在风险，但这些风险需要与能够在实验中测试疫苗而无需等待人们自然感染的巨大优势进行权衡。我们网络的核心是与这些LMIC的科学家密切合作，向监管机构、政策制定者和公众宣传这些研究的价值，然后支持科学家进行研究。开发一种新的疫苗通常需要20年时间，成本超过10亿GB。利用实验性挑战研究，可以获得明确的结果，表明疫苗只对少数志愿者有效或无效--可能是10到100名志愿者。以这种方式进行挑战研究可以在原则上证明疫苗的有效性。相比之下，需要证明疫苗有效的实地研究可能是巨大的，通常涉及数千人，费用是人类挑战研究的数倍。从伦理上讲，需要仔细权衡人类挑战的好处和致病意图。这将可以测试的感染范围缩小到那些疾病相对轻微或可预测和自我限制的疾病，或者那些可以通过现有药物或支持性护理轻松可靠地治疗的疾病。英国正在进行的人类感染研究的例子包括流感、呼吸道合胞病毒、鼻病毒、伤寒、疟疾、细菌性肺炎和百日咳。尽管有一些问题需要克服，但如果能够应对人类的挑战，针对寨卡病毒、登革热和MERS等新兴病毒的疫苗开发将大大加快。疫苗领域正在进入一个非常令人兴奋的阶段，因为许多从动物实验中产生的免疫学概念现在已经准备好在人类身上进行测试。目前，英国各地的组织--伦敦、牛津、利物浦、约克、诺丁汉和南安普顿--在没有提供相互支持的结构的情况下开展此类研究，面临着道德和监管方面的挑战。我们不仅在实验技术方面，而且在如何克服监管和安全工作做法的巨大但必要的负担方面，都有很多需要相互学习的地方。有一些小组致力于研究类似的感染，但它们之间不共享试剂、测试的病原体或其他资源。我们提议的网络将汇集所有这些专业知识，以我们从公众获得的支持为基础，用信息丰富和控制良好的人体研究取代动物实验，从人类感染志愿者网络和监管/伦理网络带来统一的声音，以巩固英国作为疫苗开发最宽松和最支持环境的地位。我们将通过联合努力做到这一点：通过电话、面对面举行定期会议，并相互提供实际支持。我们将在网络内组成联合体，申请资金提供核心材料和资源。除了加速疫苗开发，HIC-Vac还将合作解决有关人类感染的基本科学问题，这些问题只能从英国国内和国际上的挑战研究中获得。所有这些工作都与困扰LMIC的疾病有关；如果得到资助，我们拟议的网络将因此为改善全球健康做出重大贡献。

Although vaccines save millions of lives around the globe every year, there are many infectious diseases that still kill large numbers of people that are still not preventable by vaccination. This is especially true in low and middle income countries (LMIC) where even basic hospital treatment is unavailable, and the only realistic option is to prevent infectious diseases by finding new and economically viable vaccines. For several hundred years the UK has led the world in making original scientific discoveries by human experimentation. Although there are clearly risks in infecting people with pathogens, these risks need to be balanced against the great advantage of being able to test vaccines experimentally without waiting for people to acquire infections naturally. Central to our network is a close collaboration with scientists in these LMIC to advocate for the value of these studies with regulators, policy makers and the public and then to support scientists to perform the studies.Developing a new vaccine typically takes 20 years and costs over £1bn. Using experimental challenge studies, definitive results can be obtained showing that a vaccine works or does not work with only a few volunteers - perhaps 10 to 100. Conducting challenge studies in this way allows proof in principle of vaccine efficacy. By contrast, field studies that are needed to prove that a vaccine works can be vast, usually involving thousands of individuals and costing many times more than a human challenge study.Ethically, the benefits of human challenge need to be weighed carefully against the intention to cause disease. This narrows the range of infections that can be tested to those where the disease is relatively mild or predictable and self-limiting, or diseases that can be easily and reliably treated by existing drugs or supportive care. Examples of human infection studies that are on-going in the United Kingdom include influenza, RSV, rhinovirus, typhoid, malaria, bacterial pneumonia and whooping cough. Although there are problems to be overcome, vaccine development for emerging viruses such as Zika, dengue and MERS would be greatly accelerated if human challenge could be performed.The field of vaccines is entering a very exciting stage in that many immunological concepts that have emerged from studies in animals are now ready for testing in man. At present the groups around the UK, in London, Oxford, Liverpool, York, Nottingham and Southampton, face the ethical and regulatory challenges to mounting such studies without a structure to provide mutual support. We have a great deal to learn from one another regarding not only experimental techniques but also how to overcome the large but necessary burden of regulation and safe working practices. There are groups working on similar infections but not sharing reagents, tested pathogens or other resources between them. Our proposed network will bring together all of this expertise, build on the support that we have from the public in replacing animal experimentation with informative and well controlled human studies, bringing a unified voice from the human infection volunteer network and regulatory/ethical networks to reinforce the UK's position as the most permissive and supportive environment for vaccine development.We will do this by uniting our efforts: holding regular meetings by phone, face to face and providing one another with practical support. We will form consortia within the Network to apply for funding to provide core materials and resources. In addition to accelerating vaccine development, HIC-Vac will collaborate to address fundamental scientific questions about human infection that can only be obtained from challenge studies both within the UK and internationally. All of this work is relevant to diseases that afflict LMIC; if funded, our proposed network will therefore contribute very substantially to improving global health.