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The University of Southampton

Research Group: Infection and Immunity Research group

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Key strengths lie in our ability to exploit cross-cutting research and to study disease mechanisms at the molecular level all the way though to studies in man. Our over-arching aim is to develop new diagnostic tools, treatments and prevention strategies for infectious diseases, with emphasis on rapidly lethal and chronic infections.

Infection and Immunity Research

Research focus

Research within the Infectious Diseases and Molecular Microbiology group is focussed on investigation of pathogenesis, prevention and diagnosis of infectious diseases. The research covers several complementary areas: virology/virus genomics, bacterial pathogenesis, molecular epidemiology, diagnostics, global health, experimental human challenge, early and late phase clinical trials. Our over-arching aim is to develop new diagnostic tools, treatments and prevention strategies for infectious diseases, with an emphasis on rapidly lethal and chronic infections.

1. Virology

Our virology research is focused on RNA viruses and includes both short term rapidly developing infections such influenza, common cold and norovirus as well as the longer term chronic infections caused by Hepatitis C virus and HIV. The work builds on strengths in respiratory medicine, gut/epithelial biology, hepatology and global health. The hepatitis grouping studies clinical and basic aspects of hepatitis C and B, with national and international partnerships. We have pioneered the understanding of natural killer cells and innate immunity in hepatitis C, and are currently refining models to understand the fine control of NK cells in the context of viral infection based on our novel observations of their control by peptide. We are also active in national studies for the understanding of and treatment of hepatitis C with the new directly acting anti-viral agents.

2. Bacterial pathogenesis

Research is primarily centred on bacterial pathogenesis and the pre-clinical development of vaccines. Our work focuses on the major causative organisms of bacterial meningitis and sepsis, tuberculosis, sexually transmitted disease, keratitis and inflammatory skin conditions. Current studies involve development of novel in vitro primary cell culture systems and the application of several ‘omics’ platforms to the interfaces between molecular and cellular microbiology, immunology and biochemistry/biophysics, capitalising on a strong national and international collaborative network. Our overall goal is to translate our basic and applied research to tackle unmet needs of human and animal infectious diseases.

3. Molecular Epidemiology

Research focuses on the molecular epidemiology of bacterial infections. There are strong multi-disciplinary links between public health, epidemiology, microbial communities and biofilms themes. Post-genomic technologies are exploited to investigate the relationships between different microbial species at the genomic level. Emphasis lies in the study of disease potential, antibiotic resistance and the identification of therapeutic targets particularly in health care associated infections. In addition, genomic studies are used to investigate transmission dynamics, sexual networks and the evolutionary origins of bacterial species.

4. Novel Diagnostics

Research into novel diagnostic tools is focused on the development of improved diagnostic methods for the detection of both bacterial and viral infections. Point-of-care tests are currently being developed for respiratory (TB) and sexually transmitted infections. This includes multi-centre studies within the UK as well as international collaborations (the University of Melbourne, the University of Cape Town and the Kwazulu-Natal Research Institute for Tuberculosis and HIV).

5. Global Health

Global Health research is focussed on Infectious Diseases Epidemiology, in particular HIV transmission dynamics, and the impact of antiretroviral drugs on HIV transmission, pregnancy and infant outcomes, sexual behaviour and partnership change. With the roll-out of HIV treatment and care, HIV has become a chronic disease and questions regarding aging, co-morbidities of HIV with NCDs are being addressed. The data that underpin this work come from sub-Saharan Africa, in particular South Africa, but the results have bearing for many resource-limited settings. Fieldwork to collect the necessary data, and samples for investigations at basic science level, requires scientific and logistical expertise; the multidisciplinary research environment at Southampton is well-placed to support these activities. Several randomised clinical trials are in progress.

6. Experimental human challenge

Controlled infection is used in Southampton to investigate pathogenesis and prevention of infectious disease. This work is performed within the NIHR Wellcome Trust Clinical Research Facility with a focus on Neisseria, and respiratory viruses including RSV and influenza. Southampton collaborates with colleagues in Oxford to use malaria challenge to investigate new vaccines.

7. Clinical vaccine trials

Clinical research is focused on the prevention and management of severe bacterial disease and respiratory virus infection in children and adults. Themes include trials evaluating the safety and efficacy of candidate vaccines against meningococcal disease and pandemic influenza strains including H7N9. Phase 1 studies of new influenza and malaria vaccines occur in the MHRA phase 1 accredited Southampton NIHR WTCRF in collaboration with the Jenner Institute, University of Oxford. Additionally there is evaluation of new diagnostic and management strategies for hospitalised adults and children with sepsis and influenza. There are strong links with Public Health England including the molecular laboratory at University Hospital Southampton and national reference laboratories.

Key achievements

The group has discovered a new mechanism for regulating NK cell activation which underpins their ability to control HIV-1 and HCV infection.

Our studies of bacterial populations have informed national vaccination policy, for example by demonstrating changes in serogroup and genotype prevalence among carried and disease-causing meningococci and pneumococci during vaccine implementation in the UK.

We were the first to show that some meningococcus serotype C glycoconjugate vaccines rely on persistence of antibody levels rather than immunological memory for sustained protection, identifying a potential risk for long term protection after vaccination.

Using molecular approaches, the Group has developed a transformation system for Chlamydia trachomatis, permitting genetic manipulation of the pathogen for the first time.

The Group is developing improved approaches for immunodiagnosis of human TB, and has provided the first evidence of how tuberculosis causes cavitation by showing that MMP-1 drives immunopathology, suggesting that inhibition of MMP activity is a realistic goal as adjunctive therapy in TB.

The Group has made key contributions to understanding innate immune mechanisms in humans including the first demonstration that surfactant protein D (SP-D) interacts with human rhinovirus and HIV-1.

Collaborations and enterprise

In collaboration with GSK, the Group has developed vaccine strategies for effective functional antibody induction to meningiococcus serotype-B pathogen-derived antigens for which no current candidates exist.

Through an international collaboration involving The Wellcome Trust Sanger Institute, the Group has undertaken whole genome analysis of diverse C. trachomatis strains to identify phylogenetic relationships masked by current clinical typing, with implications for monitoring and epidemiological tracking of infections.

Our research into novel diagnostics includes multi-centre studies in UK, as well as international collaborations, including the University of Melborne, The University of Cape Town and the Kwazulu-Natal Research Institute for Tuberculosis and HIV.

Our work on pneumococcal genotype in carriers has led to a collaborative infectious diseases network in South East Asia, with high level strategic partnerships for research and training with A*STAR Singapore and the University of Malaysia.

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