HIC-Vac Network additional funding

The UK is a global leader in making original scientific discoveries by human experimentation. Human infection challenge of volunteers carries risks, but these need to be balanced against the great advantage of being able to test vaccines and treatments experimentally without waiting for people to be naturally infected. 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. Central to this aim is close collaboration with scientists in these LMICs, who can advocate for the value of these studies with regulators, policy makers and the public.

Developing a new vaccine used to take 20 years and cost over £1bn. This situation has changed during the COVID pandemic but, by using experimental challenge, definitive results can be obtained much quicker showing that a vaccine works or does not work with only a few volunteers - perhaps 10 to 100 - being given the vaccine and a similar number being given control inoculation. Conducting challenge studies in this way allows proof in principle of vaccine efficacy. By contrast, the 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 harm that may be caused to the volunteers. 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 and paratyphoid, 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 in a very exciting stage in that many immunological concepts that have emerged from earlier studies can now been applied in fresh situations. At present the members of the HIC-Vac consortium in the UK (London, Oxford, Liverpool, York, Nottingham and Southampton) and overseas have faced many ethical and regulatory challenges to mounting these studies and are keen to share their experience and 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.

We will do this by bringing our efforts together: holding regular meetings by phone, face to face and providing one another with practical support. HIC-Vac's main strength is that we can distribute funding to members, so enabling this work. In addition to accelerating vaccine development, our Network will collaborate in addressing fundamental scientific questions about human infection that can only be obtained from challenge studies both within the UK and globally (especially LMIC regions).

Vaccines are amongst the most practical and cost-effective ways of mitigating the impact of infectious disease, especially in LMIC/resource-poor settings. Although they already prevent an enormous number of serious and lethal infections, new or improved vaccines are needed. Animal studies are of limited value and human field trials are both expensive and prone to failure.

Human infection challenge (HIC) is an excellent way to expedite vaccine development, enabling vaccines to be tested at reduced cost while providing abundant information about disease pathogenesis and mechanisms of protection. Going back to the time of Edward Jenner, the UK has had a strong tradition of HIC and continues to have a relatively supportive legal, regulatory, ethical and reputational environment.

Our network will draw upon the extensive HIC experience of the UK's many research groups using pathogens such as SARS-CoV2, RSV, influenza, rhinovirus, typhoid/paratyphoid, malaria, Neisseria, pertussis, pneumococcus, BCG, leishmania and hookworm. It will draw together our collective experience and share best practice, supporting the development of new research initiatives in testing vaccine safety and efficacy. The network will bring in new investigators and will provide resources to promote the ethical, legally compliant and safe use of HIC.

By distributing pump-priming funds, we will catalyse areas of study that extend the use of HIC, enabling substantial grant applications to be made. Most importantly, it will allow comparison of vaccine effects in UK volunteers with those in countries such as Malawi, India, Vietnam and Kenya. The network will work with commercial partners to promote the development and use of HIC in vaccine development, communicating the advantages of HIC to regulators, policy-makers and the public. Our network will thereby keep the UK at the forefront of global vaccine research.