Human infection challenge vaccine (HIC-vac) network 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. The Global Challenges Research Fund (GCRF) supports cutting-edge research to address challenges faced by developing countries. The fund addresses the UN sustainable development goals. It aims to maximise the impact of research and innovation to improve lives and opportunity in the developing world.