Professor Hazel Dockrell, Dr Helen Fletcher and Dr Gregory Bancroft are all part of TBVAC2020 and based at the London School of Hygiene and Tropical Medicine (LSHTM), within the department of Immunology of Infectious Diseases (IID). They have been actively involved in finding immune correlates of protection, implementation of new TB vaccines and testing of vaccine candidates in murine models. These three laboratories are a part of the TB Centre, an extensive network of TB researchers and collaborators based at LSHTM.
The Dockrell group is examining vaccine-induced immune responses that may predict immune protection against tuberculosis (TB), and how co-infection and co-morbidity can affect such immune responses. A good knowledge of correlates of protection could predict the efficacy of novel vaccines at early stages of development and help identify the most promising candidates for vaccine trials. The Dockrell group investigates T cell immunity and cytokines that are released in response to BCG vaccination in UK infants, and also compares how the immune response to BCG in the UK differs from that in Africa where the vaccine is less effective. Professor Dockrell and her group are investigating mechanisms that regulate the production of immune-related proteins, starting from gene regulation (epigenetics), gene expression (transcriptomics), cell phenotypes (flow cytometry) and finally protein release. Secondly, the group is investigating whether BCG can modulate epigenetic changes of inflammatory genes in vitro. The Dockrell group is focusing on genes and cells that play a crucial role in polarisation of the immune responses and that could affect vaccine efficacy. The Dockrell laboratory is also using the mycobacterial growth inhibition assay in BCG-vaccinated infants and patients with latent TB infection and helminth infection. Members of the Dockrell group include Steven Smith, Mateusz Hasso- Agopsowicz and Shaheda Anwar.
The Bancroft laboratory was funded by TBVAC2020 to provide preclinical animal models to evaluate new TB vaccine candidates. The Bancroft group does not generate themselves these candidates, but it is an independent testing centre for vaccine developers, providing valuable head to head comparisons of candidates from across laboratories in the consortium. The group has two tasks, firstly to evaluate residual virulence properties of new live attenuated vaccines in the murine SCID model of immunodeficiency. Secondly, the group provides standard models of vaccination and pulmonary challenge with virulent M. tuberculosis in mice to study vaccine efficacy in vivo. Felipe Cia, an experienced investigator in the use of murine models of bacterial infection in aerosol Category 3 containment is the person performing these tasks.
The Fletcher group investigates the impact of host-immunity on TB vaccine efficacy. A major focus of the group is understanding immunity of people living in high TB incidence countries. In addition, the Fletcher group investigates immunity using the mouse model and aims to develop animal models of TB disease better able to predict TB vaccine efficacy in clinical trials.
The TB Centre at the London School of Hygiene & Tropical Medicine brings together more than 120 laboratory scientists, clinicians, epidemiologists, statisticians, public health specialists and policy-makers. The common goal of all scientists at the TB Centre is to reduce the global burden of TB, through high quality research, education and knowledge translation.
Through consultancy work, research meetings, seminars and journal clubs, members of the TB Centre disseminate their work and generate new ideas. Members of the TB Centre are global leaders in areas including:
- clinical trial design;
- tracing of TB transmission using molecular tools;
- host-pathogen interactions;
- development and implementation of new diagnostics mathematical modelling;
- health economics;
- health systems research.
The TB Centre works in more than 20 countries with high prevalence of TB across Asia, Africa and Latin America, and all researchers of the centre are strongly integrated with local academic institutions, governments and international organisations.