Infection, Immunity and Inflammation

The goal of the AHSC Infection, Immunity and Inflammation Programme is to transfer novel research developments into new diagnostic tools and therapeutic interventions for the local and global patient population.

Multidisciplinary research and training programmes serve to educate the next generation of scientists and health professionals. Jointly working with industry will accelerate the implementation of novel therapies as routine treatment.

Partnership working between academic institutions and NHS trusts is key to efficiently enrol patients into research studies and test new types of therapies in clinical trials. The development of the Institute of Immunity and Transplantation (IIT) and the Bloomsbury Research Institute (BRI) are two strategic initiatives of the AHSC to create world-leading centres for translational science.

We will bring together researchers, clinicians, nurses, patients and regulatory experts to achieve the following four objectives:

  • Develop novel immune interventions to treat disease;
  • Improve the prevention and control of infection;
  • Implement new therapies for inflammatory conditions;
  • Establish next generation diagnostics underpinning personalised medicine

Work stream - Immune interventions to treat disease


Objectives
We aim to develop novel immune-enhancing interventions for the treatment of cancer and infection, and tolerance-inducing strategies to treat autoimmunity and enable long-term function of conventional and bioengineered tissue/organ transplants.

Key achievements

  • Complete immunotherapy trials to control cancer and chronic infection
  • Develop new biological therapies for the treatment of autoimmune conditions
  • Demonstrate feasibility of bioengineered organ transplantation

Work stream - Prevention and control of infection


Objectives
A major challenge in tackling emerging infections is the widespread and varied nature of the threat. We will combine the expertise of UCL and the London School of Hygiene and Tropical Medicine to jointly develop the Bloomsbury Research Institute (BRI) as Europe’s largest grouping of infection-related researchers. The BRI will integrate excellence in pathogen biology with expertise in human genetics, mathematical modeling, population biology, clinical sciences and public health policy to develop tools to predict, map, and overcome newly emerging infections.

Key achievements

  • Integrate pathogen sequencing into routine diagnostic protocols, enabling rapid detection of drug resistance mutations
  • Implement point of care HIV testing in the UK and developing world
  • Develop novel gene therapy approached for control of HIV infection

Work stream - New therapies for inflammatory conditions
 

Objectives
We plan to extend our leadership in the development of biomarkers, biologic therapies and drug discovery for inflammatory conditions. We will focus on amyloidosis, scleroderma and rheumatoid arthritis to take advantage of our academic and clinical leadership in these conditions.

Key achievements

  • Combine small molecule and antibody therapy for treatment of all types of systemic amyloidosis
  • Perform clinical trials of new biological therapies in scleroderma
  • Develop biomarkers to stratify treatment of inflammatory arthritis

Work stream - Next generation diagnostics underpinning personalised medicine


Objectives
We will bring together the world-class clinical science and informatics expertise of the partners to drive the next generation diagnostics based on the effective integration of genetic, functional and clinical data.

Key achievements

  • Link genetic, phenotypic and functional abnormalities to improve diagnosis and treatment of immunodeficiency
  • Exploit national infection data, electronic health records and novel statistical approaches to understand the epidemiology and to control of infectious threats

Case study: New vaccine to prevent infection in transplant patients


Background
Cytomegalovirus (CMV), part of the herpes family of viruses and one of the most common viral infections, is a major infectious problem after organ transplantation. It is estimated that around 6 of every 10 adults in the UK have been infected by CMV, usually through contact with young children. It is typically unnoticed in healthy people because their lymphocytes keep the virus under control. However, the virus can be serious when it develops or reoccurs in certain vulnerable groups, particularly those with weakened immune systems such as organ transplant recipients, people with HIV and unborn babies. CMV is sometimes referred to as the ‘Toll of Transplantation’ because of the high level of serious disease it can cause in this patient group, including pneumonia, lung complications and liver infection.

Project
A team of scientists and doctors from member organisations UCL and the Royal Free London NHS Foundation Trust, led by UCL’s Professor Paul Griffiths, have developed a vaccine that could potentially target CMV and carried out a Phase II proof-of-concept study.

140 Royal Free patients awaiting transplantation of a kidney or of a liver were recruited to the trial. Half of these patients had had natural infection in the past, whereas half had never seen CMV before. After informed consent, they were randomised to receive the vaccine or a placebo. 78 of them proceeded to transplant and so had their CMV biomarkers measured following the operation.

Results

The results of this Phase II proof-of-concept study showed that a vaccine preparation moderated the severity of CMV infection in patients waiting for kidney and liver transplants and, in some cases, may have interrupted transmission of the virus from donor to recipient.

All 67 patients given the vaccine responded by making antibodies against the CMV protein contained in the vaccine. The average quantity of antibodies made by the vaccine group was very significantly increased compared to the recipients of placebo. The level of these antibodies declined a little with time, but the vaccine recipients still had antibody levels which were significantly greater than the placebo recipients when they were called to transplant.

Although this trial only examined transplant patients, it is expected that this type of vaccine could also help other groups vulnerable to CMV such as pregnant women. These results have encouraged multiple pharmaceutical companies to accelerate the development of their CMV vaccine.

Programme leadership


Professor Hans Stauss
Programme Chair- Infection, Immunity and Inflammation
Academic Health Science Centre

Links
 

Bloomsbury Research Institute
Institute of Immunity and Transplantation
UCL Cancer Institute
UCL Institute of Child Health
UCL Institute for Liver and Digestive Health
The Francis Crick Institute