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Dr Stephen Cose

Associate Professor

MRC/UVRI and LSHTM Uganda Research Unit
Plot 51-59 Nakiwogo Road
Entebbe
Uganda

My current research goal is to apply my expertise in fundamental cellular immunology to the investigation of tuberculosis in Uganda, a setting in which this disease is still highly endemic. In my previous posts I undertook research into lymphocyte migration and trafficking, studies which were performed in mice and gave me key skills in isolating lymphocytes from tissues, multiparameter flow cytometry and immunofluorescence techniques. Since moving to Uganda my focus has now changed to human Immunology. Previous studies have included an MRC funded project to look at whether a latent TB infection in mothers affects their infant’s response to BCG. This is an important area of research as BCG is not as protective in settings such as Uganda, and this project aimed to understand why this may be the case. Other completed studies were the non-specific effects of BCG immunisation, where we conducted a delayed BCG trial to examine whether BCG has non-specific beneficial effects in healthy newborns. I have a major interest in the role that B cells play in Mycobacterium tuberculosis (M.tb) infection, TB disease in pregnancy, and in studying tissue-specific T- and B-cell responses to M.tb infection, in health and disease.

Affiliations

Department of Clinical Research
Faculty of Infectious and Tropical Diseases

Centres

TB Centre

Teaching

I have over 15 years of teaching fundamental and tropical immunology to undergraduate (BSc/BVM/MBBCh) and postgraduate students (MSc/MMed/PhD).

My teaching experience has enabled me to design and run the “Immunology in the Tropics” course in Uganda (www.muii.org.ug). Along with implementing and running the course, I also lecture on the fundamental immunology module and coordinate international faculty for specialised, disease-specific components. This course has met with high acclaim and now recruits participants from at least 14 countries across sub-Saharan Africa, as well as the UK and Europe, with applications consistently outstripping available places. This course consists of one week of disease-specific lectures, tutorials, journal clubs and seminars. The second week involves wet lab practicals, where attendees get experience in using relevant diagnostic assays and other immunological assays currently in use around the world for that disease.

I have also developed a short course in Tropical Immunology, aimed at clinicians who are at the front line of diagnosis and clinical trials, but often do not understand the immunological outcomes of the diseases they are diagnosing or researching. This teaching module is delivered to staff and students at the MRC/UVRI and LSHTM Uganda Research Unit. Feedback from clinicians undertaking this course has been excellent.

Research

My current research interests are in “TB at the ends of life”, and I have two ongoing studies in this area:

TB in Pregnancy

In this study we are interested in determining immune responses and outcomes in children born to mothers with active TB. This is a completely understudied area, but available epidemiological data suggests that infants born to such mothers have the same mortality and morbidity as infants born to HIV positive mothers in the pre-ART era. This remains the case even if mothers are started on TB therapy during pregnancy. We will examine vaccine responses in infants over the first year of life.

Tissue-specific responses to TB infection

Here we are undertaking postmortem studies on individuals dying from TB, and in individuals who were otherwise healthy at the time of death. We believe that to fully understand a disease, and to design more effective vaccines, we must study the immune response at the site of infection. For M.tb, this is in the lungs. Our central hypothesis is that lung tissue resident cells are deficient in subset, function and anatomic location in individuals with active TB infection, compared to those with a LTBI, suggesting a major role for these subsets in the control of TB. This is a first-of-its-kind study and we will be able to compare tissue cell subset, function and anatomic location in unprecedented detail, for the first time in humans, using the latest cutting-edge immunological techniques.

Research Area
Clinical trials
Helminths
Innate immunity
Immunisation
T-cell immunology
Vaccines
Bacteria
Immunology
Vaccinology
Capacity development
Virology
Disease and Health Conditions
Tuberculosis
Schistosomiasis
Country
Uganda
Region
Sub-Saharan Africa (developing only)

Selected Publications

Kaposi's sarcoma-associated herpesvirus T cell responses in HIV seronegative individuals from rural Uganda.
Nalwoga, A; Roshan, R; Moore, K; Marshall, V; Miley, W; Labo, N; Nakibuule, M; COSE, S; Rochford, R; NEWTON, R; Whitby, D;
2021
Nature communications
BCG-induced non-specific effects on heterologous infectious disease in Ugandan neonates: an investigator-blind randomised controlled trial.
PRENTICE, S; Nassanga, B; WEBB, EL; Akello, F; Kiwudhu, F; Akurut, H; ELLIOTT, AM; Arts, RJ W; Netea, MG; DOCKRELL, HM; COSE, S; Delayed BCG Study Team,;
2021
The Lancet. Infectious diseases
Mycobacterium tuberculosis infection is associated with increased B cell responses to unrelated pathogens.
Kimuda, SG; Andia-Biraro, I; Sebina, I; EGESA, M; Nalwoga, A; Smith, SG; Bagaya, BS; Levin, J; ELLIOTT, AM; RAYNES, JG; COSE, S;
2020
Scientific reports
Post-immunization leucocytosis and its implications for the management of febrile infants.
PRENTICE, S; Kamushaaga, Z; NASH, SB; ELLIOTT, AM; DOCKRELL, HM; COSE, S;
2018
Vaccine
Rethinking Schistosomiasis Vaccine Development: Synthetic Vesicles.
EGESA, M; Hoffmann, KF; Hokke, CH; Yazdanbakhsh, M; COSE, S;
2017
Trends in parasitology
Immunology in Africa.
COSE, S; Bagaya, B; Nerima, B; Joloba, M; Kambugu, A; Tweyongyere, R; Dunne, DW; Mbidde, E; KALEEBU, P; ELLIOTT, AM;
2015
Tropical medicine & international health
Circulating B-lymphocytes as potential biomarkers of tuberculosis infection activity.
Sebina, I; Biraro, IA; DOCKRELL, HM; ELLIOTT, AM; COSE, S;
2014
PloS one
Immune cell phenotype and function patterns across the life course in individuals from rural Uganda.
Nalwoga, A; Nakibuule, M; Roshan, R; Kwizera Mbonye, M; Miley, W; Whitby, D; NEWTON, R; Rochford, R; COSE, S;
2024
Frontiers in immunology
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