The VALIDATE Network - Vaccine development for complex intracellular neglected pathogens
VALIDATE is an international network of vaccine researchers focused on four pathogens causing diseases with significant impact on low and middle-income countries: tuberculosis, leishmaniasis, melioidosis and leprosy.
Our seminars highlight some of the important research being undertaken by our extensive community of researchers. We will put details of any upcoming seminars on this page.
Dr Xiao will be discuessed the Immunology of latent TB infection (LTBI) and active TB disease, the granuloma formation and T cell medicated immunity and the immunology behind T cell-mediated immunity tests.
In an upcoming publication in Nature Biotechnology, Dr Sheila Keating and her team have demonstrated the technology to capture entire immune repertoires from infected or vaccinated individuals, to be used to treat difficult to treat infections - and have demonstrated this work with COVID and respiratory bacterial infections. In this talk, Sheila will describe the technology and will map out potential pathways for developing passive immune therapeutics that will not only treat but also help to prime immune responses to protect against future infections. Location: Online via Microsoft Teams
Speaker: Dr Sheila Keating is a VALIDATE Network Investigator Adjunct Associate Professor at GigaGen and the University California San Francisco. Over the past 15 years, Sheila's work has focused on understanding cellular and humoral immune responses to vaccines and infectious diseases and, more recently, has focused on using high throughput immune assays to measure biomarkers of immune response or pathology in a number of studies ranging from HIV, HCV, HBV vaccine breakthrough, Chagas, West Nile Virus, cardiovascular disease, neuropathology and many other areas.
COVID has provided a stark example of pathogenic mutation. The variation of the impact of infection on the population similarly shows that human responses are variable. This highlights a key need in vaccinology of identifying and developing technologies that can address diversity whilst maintaining safety and achieving cost-effectively. In this session, Graham Clarke explores the options and particularly highlight ImmBio’s approach, exemplified by its lead development against Streptococcus pneumoniae, a good example of a bacteria in circulation with a wide array of genotypes. Whilst there are products available providing good protection against specific serotypes, as defined by the polysaccharide capsule used in the current class of vaccines, ImmBio’s focus is a multiple-protein approach. A new approach raises new regulatory and manufacturing challenges but again drawing on COVID experience, vaccinology may be able to able to benefit from a paradigm shift in addressing risk and benefit, enhancing the attractiveness of investing in new vaccines.
Speaker: Graham Clarke is ImmBio’s Chair and previously its CEO. Originally a biophysicist, he has held senior-level positions including at SmithKline Beecham, GSK and GE Healthcare. He is now a non-executive on a number of boards, including the UK’s Medicine Discovery Catapult and NHS Health Research Authority. He has also been a member of the UK government’s COVID therapeutic task force.
Dr Maria Adelaida Gomez is VALIDATE Network Investigator and a Coordinator at the Molecular Biology and Biochemistry Lab at CIDEIM in Cali, Colombia. Adelaida is currently working to unravel the host-pathogen interactions and underlying mechanisms that determine the outcome of human Leishmania infections and therapeutic responses, towards the identification of host and parasite biomarkers of treatment outcome, and intervenable host functions to optimize therapeutic strategies.
Giorgio Colombo is Professor of Organic Chemistry at the Dept of Chemistry, University of Pavia. Prof Colombo has authored or coauthored more than 150 scientific publications in international journals, and works to integrate molecular dynamics, computational physical-chemistry and bioinformatics approaches to study the dynamics and specificity of protein-ligand recognition and binding.
Louise Gourlay is an Assistant Professor in Biochemistry at the Department of Biosciences at the University of Milan, Italy. Asst Prof Gourlay is a structural biologist and biochemist with a principal interest in using 3D structure information, obtained via X-ray crystallography, to re-engineer protein antigens/epitopes from Burkholderia pseudomallei, to improve their potential use as immunogens in a melioidosis vaccine and on developing novel, immunodiagnostic tests for emerging infections.
Professor Samantha Sampson is a TB researcher and heads the Host-Pathogen Mycobactomics Research Group at Stellenbosch University. The group aims to gain a better understanding of how the pathogen Mycobacterium tuberculosis interacts with its host to cause disease.
Dr Jomien Mouton is a post-doc in Prof Sampson's Host-Pathogen Mycobactomics Research Group at Stellenbosch University and is a VALIDATE Fellow. Dr Mouton's work focuses on establishing and validating a new dual-reporter system that can be utilised to identify and isolate “persister” populations of Mycobacterium tuberculosis.
Bernardo Villarreal-Ramos is VALIDATE Network Investigator and Professor of Immunology at the University of Aberystwyth and the Animal and Plant Health Agency (APHA), UK with a research focus on Tuberculosis, animal models, vaccines and T-cells.
Amanda Gibson is a VALIDATE Network Associate and Lecturer in Innate Immunology at Aberystwyth University whose research interests lie in underpinning early events required for establishing infection; the interaction between mycobacteria and host cells, particularly with the innate immune system at the point of recognition and uptake and initial responses leading to disease.
Associate Professor Hiro Goto is a VALIDATE Network Investigator based at the Universidade de Sao Paulo (USP), Brazil. Hiro's research focus is on immunopathology and diagnosis of leishmaniasis.
Eduardo Milton Ramos Sanchez is a VALIDATE Network Associate and Post-doctoral researcher presently working at the Institute of Tropical Medicine of Sao Paulo, USP, Brazil. Eduardo has been involved in purification and production of recombinant antigens for the development of serological tests for leishmaniasis and Malaria and vaccines for Bovine mastitis.
Speaker: Mary Burtnick is a Network Investigator and Associate Professor based in the University of Nevada, Reno School of Medicine. Mary has nearly two decades of experience working with pathogenic Burkholderia species and her current research focuses on identification of antigens expressed by Burkholderia pseudomallei that can be used to develop novel vaccines, diagnostics and immune assays to combat melioidosis.
Prof Siobhán McClean is an Associate Professor at School of Biomolecular and Biomedical Science, UCD. Prof McClean has a research interest in host pathogens associated with respiratory pathogens that cause opportunistic infections and in identifying vaccine antigens that are protective against Burkholderia pseudomallei.
Dr Julen Tomás Cortázar is a postdoctoral researcher at UCD. He is leading part of a project funded by Wellcome Trust agency to develop a vaccine against Melioidosis caused by the Gram-negative bacteria Burkholderia pseudomallei.
TB kills more people than any other infectious disease. The efficacy of the only available vaccine, BCG, is highly variable and lowest in high burden settings. The McShane group is developing novel TB vaccine candidates by identifying novel antigenic targets and exploring novel routes of immunization.
TB vaccine development is challenging given the lack of defined immunological correlates of protection. Class II restricted T cells are critical for protective immunity but may not be sufficient. Dr Tanner provided an update on functional mycobacterial growth inhibition assays and on a role for antibodies in protective immunity.
Immune correlates of risk of TB disease have recently been identified in human clinical trials. These correlates indicate that, years before TB disease develops, there is alteration in the host-immune environment which is associated with risk of TB disease. Perhaps these alterations render the immune environment permissive to mycobacterial infection or increased growth, or perhaps they reduce the efficacy of the BCG vaccine? Back translation of immune correlates of risk into animal models will enable us to address these questions and model the immune response of those individuals at greatest risk of TB disease.