Vaccines for vulnerable populations

Focussing on vaccines for vulnerable populations, the Tropical Immunology Research Group study immune responses in healthy individuals to understand how to protect those with frail immune systems, such as the elderly and diabetics, from bacterial infections like E. coli and Klebsiella. Key goals include identifying immune markers of protection and designing vaccines to prevent deaths in low- and middle-income countries. Addressing antimicrobial resistance is urgent to prevent untreatable future infections.

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Infection remains one of the major causes of death globally, and increasing rates of diabetes, a key risk factor for infection, means new tools such as novel therapeutics and effective vaccines are urgently required. My research uses expertise in microbiology and immunology in tropical countries to address key questions that advance treatment of bacterial infection and vaccine discovery.

Specific diseases of interest include melioidosis, scrub typhus, tuberculosis and COVID-19. In addition, we are focusing on the role of metabolic dysfunction in impaired immunity in people with Type 2 diabetes to intracellular pathogens.

Burkholderia pseudomallei is a Gram negative bacterium which causes melioidosis in humans. Melioidosis is a common cause of illness and death across tropical regions yet its international profile is low. The known risk factors include diabetes, alcoholism and renal disease and the range of presentations includes pneumonia, liver and splenic abscesses and septic shock.

In 2020 my laboratory merged with four other laboratories at Medawar, Oxford to form a "megalab" tackling T cell immunity to SARS-CoV-2 alongside our other projects. I am joint Chief Investigator of the UK PITCH Study (Protective Immunity for T cells in Healthcare workers) with Prof Paul Klenerman which is examining the immune response to the Pfizer BNT162b2 and Oxford-AstraZeneca vaccines. The PITCH Study will also be a healthy control comparison cohort for the national OCTAVE Study (Observational Cohort-study of T-cells, Antibodies and Vaccine efficacy), a national study of vaccine response in UK patient groups with immunocompromise, with Prof Eleanor Barnes as the Oxford lead. I am also collaborating with scientists in Vietnam, Thailand, Indonesia, Bangladesh and Kenya to evaluate responses to SARS-CoV-2 infection and vaccines in other populations. We will then take the learning and assay development from SARS-CoV-2 and apply it to melioidosis and other global diseases.

Key questions currently being addressed include:

• What is the role of T cells in protective immunity against COVID-19?
• Why are people with diabetes so susceptible to severe disease caused by SARS-CoV-2 and intracellular pathogens, such as melioidosis and TB?
• How does cellular metabolism influence immune cells function in health and in diseases such as diabetes, and how can we intervene to improve the immune systems of people with diabetes?

The Tropical Immunology laboratory at the Peter Medawar Building in Oxford was established in 2015, and the growing team includes post-doctoral immunologist Dr Barbara Kronsteiner-Dobramysl and DPhil students Patpong (Palm) Rongkard, Dr Mohammad Ali and Sandra Adele. In this laboratory we use cutting-edge approaches to characterise the immune response to tropical pathogens, and have set up a core immunometabolism facility including a Seahorse flux analyser in the BSL3 laboratory.

We are also working with Dr Fazle Rabbi Chowdhury in Dhaka, Bangladesh on studies of diabetes and infection, and working with collaborators worldwide to develop laboratory research capacity. Other activities include contributing to the Wellcome Trust’s “Foreign Bodies, Common Ground” exhibition and working with clinical microbiologists at multiple sites in South East Asia to standardise diagnostic microbiology lab SOPs for tropical settings. Antimicrobial resistance (AMR) is an accelerating global problem, with people in low and middle income countries (LMIC) predicted to experience the biggest burden, and I use my clinical expertise in microbiology to support global collaborative research in this domain.