Funding

Board strategy (IIB)

    Strategy

    The Infections and Immunity Board (IIB) aims to develop scientific knowledge that extends our understanding of human infectious disease, and disorders of the human immune system. This includes and is underpinned by fundamental research into human pathogens, as well as the normal development and functioning of the human immune system, which informs mechanism of disease. Working with other MRC initiatives and partners, the Board seeks to ensure that the insights it supports are translated into health benefits, and that the UK has the necessary infrastructure, skills and expertise to fulfil its aims.

    To deliver against its areas of strategic focus, listed below, the Board supports the development of strategic investments and partnerships and initiatives and is seeking to develop its portfolio of investigator-led awards through Board Opportunities. Grants meeting Board Opportunity criteria will be prioritised for consideration in Board funding decisions.

    Contents

    Global health

    Global health is a key MRC strategic aim and IIB plays an important role in developing and delivering this agenda, particularly on priority infectious diseases in Low- and Middle-Income Countries. While continuing to support research tackling the major infections, HIV, tuberculosis and malaria, we will further support high quality, innovative research in neglected tropical diseases, fungal, and emerging infections, which have major impact on the health and wellbeing of populations in resource poor settings.

    We have drawn on the opportunity afforded by the Global Challenges Research Fund to instigate new research and new research partnerships, including through a Foundation call, and supporting networks investigating the vector-borne diseases and developing vaccine preventative approaches.

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    Resistance

    Pathogens naturally evolve resistance mechanisms to drugs and this can have potentially catastrophic health implications. The importance of preventing and treating resistance in bacteria, viruses, parasites, fungi and vectors now has global recognition. A broad ‘One Health’ systems approach is required to investigate and prioritise drivers and constraints of resistance. We also need to better predict resistance emergence, develop new diagnostics, therapeutics (including novel chemistry, combinations and the negative impacts of antibiotic intervention), and effective intervention regimes, including design, behavioural changes and the potential of the microbiome as a therapeutic intervention.

    Through the IIB, the MRC has developed a cross-council, interdisciplinary approach to addressing the key challenges in antimicrobial resistance (AMR). Together with our sister research councils and other national and international partners, we are enabling researchers in the UK to undertake cutting-edge research, in collaboration with research colleagues across the globe, and to take unique approaches to AMR. Our strategy for tackling AMR focuses on identifying, prioritising and understanding the drivers of AMR and to use this knowledge to prevent infections, preserve existing antibiotics and promote the development of new therapies and interventions.

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    Preparedness

    The recent outbreaks of Ebola and Zika, bird/swine flu epidemics, and the on-going global burden of malaria, tuberculosis and HIV, illustrate the large-scale challenge that infectious diseases continue to pose to human health. A strategy of pandemic preparedness requires that strong underpinning science is present in a range of areas before infection becomes widespread. This should include pathogen biology, real time surveillance and data capture, data sharing, modelling, diagnostics, prophylactic interventions and therapeutics, as well as their bioprocessing and manufacture.

    Our work in pandemic preparedness builds on our experience in the Environmental and Social Ecology of Human Infectious Diseases initiative, established to respond to the threat from new and emerging pathogens. This ground-breaking initiative has supported novel interdisciplinary approaches to study the ecology of infectious diseases. The initiative is complemented by the Zoonoses and Emerging Livestock Systems programme, coordinated by the Biotechnology and Biological Sciences Research Council (BBSRC), which aims to minimise the health risks associated with the rapidly changing nature of livestock systems in developing countries, focusing on those risks that impact on the livelihoods and health of poor people.

    In addition to supporting research into potential threats, we also responded to disease outbreaks. When WHO declared the West Africa Ebola outbreak an emergency in August 2014 the MRC quickly engaged with funding partners, including the Wellcome Trust and the Department for International Development (DFID) to commence the first of a number of vaccine trials in the region. MRC co-funded research on the RING vaccination trial, which showed best evidence of a protective effect during the epidemic. In response to the Zika outbreak, we launched a rapid response initiative to provide novel, critical and timely insights into the nature of the virus and/or potential avenues for its management or prevention. Working with the Department of Health and Social Care (DHSC) and BBSRC through the UK Vaccines Network, we are now supporting the development of vaccines against priority pathogens.

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    Immunity and infection through the life course

    Perinatal and childhood acquisition of micro-organisms, both pathogens and the colonising microbiota, constitute major exposures that affect morbidity and mortality throughout the life course, potentially through establishing the basis of immunological homeostasis. Immunological memory is critical for maintaining naturally-evoked and vaccine-induced protection. Gradual decline of immune function with age reduces the host’s capacity to respond to infection and evoke protective responses on vaccination, and may contribute to an increase in the risk of cancer. Understanding the crosstalk between the circadian and the immune systems will allow us to manipulate clock outputs to prevent and treat inflammatory diseases in individuals at risk and better target vaccination strategies.

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    Chronic infection, co-morbidity, immunomodulation

    As our ability to manage infections increases, it will be important to deepen our understanding of chronic infections, including how persistent infections interact with and affect the host immune system over the life-course, and how the immune system might be modulated to better target persistent infections. There is also scope to study the consequences of living with latent infections, how these infections may affect the host through the life-course and what triggers emergence from latency.

    Multi-morbidity is a major challenge within the aging UK and wider population. It is important to deepen our understanding of how immune status can contribute to diseases, including the Immune Mediated Inflammatory Diseases (IMIDs), neurodegeneration and psychosis, and how infections, including commensal, invasive and co-infections, affect the host immune system over the life-course and interact with other morbidities, both communicable and non-communicable, including cancer, asthma, mental health.

    Immune-mediated inflammatory diseases (IMIDs) represent a wide range of conditions which affect specific or multiple organs and which often share both immunological and mechanistic features, but have different clinical manifestations.  The spectrum of IMIDs also include more common autoimmune and autoinflammatory disorders, such as Psoriasis, Type 1 diabetes, Rheumatoid Arthritis and Ulcerative Colitis. For the most part, research into IMIDs has been pursued in a disease-specific manner driven by clinical presentation and often focussed on the later stages of disease. As such, many of the common mechanisms regarding the initial loss of immune tolerance or early instigators of the inflammatory cascade may not yet have been fully exploited. The MRC has a number of significant investments in IMIDs, including an IMID BioBank and a number of Stratified Medicine Consortia. We are looking into ways of working with other interested partners, including industry and other funding agencies to help coordinate activity in this area. Further details of a 2017 report on IMIDs, held in collaboration with MRC, Wellcome, Juvenile Diabetes Research Foundation and Arthritis Research UK can be found in this report.

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    Data integration and systems approaches – from data to insight

    Integrating data between different classes (e.g. DNA, proteomic, etc.) and levels (e.g. cell, tissue, individual, population), can provide novel epidemiological and mechanistic insights. Models developed with these insights can be improved upon through a systems approach of iterative cycles of modelling, experimentation and refinement.

    We led a cross-council initiative to take a systems approach to understand immune function in health and disease. Two consortia were established through this initiative: “Multi-scale analysis of B cell responses in ageing” at Kings College London, and “Phenotyping immune responses in asthma and respiratory infections - a systems approach to understanding changes from childhood to adulthood” at Imperial College London and University of Manchester.

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