Immunomodulation and Vaccines
Medical Research Council
MRC/UVRI and LSHTM Research Unit Uganda
Our goal is to understand the impact of infection exposure on human immunological programming and health. Our overarching hypothesis is that chronic and cumulative infection exposure influences immunological mechanisms through active processes (during current infection), lasting epigenetic modifications, and genetic selection; that (therefore) some effects do not immediately respond to treatment; and that effects critically impact upon major health outcomes including vaccine responses and susceptibility to pathogens, allergy-related disease and metabolic conditions (Figure 8.8). The main focus of our work is on vaccine responses, addressing the role of infectious exposures in striking population differences in vaccine immunogenicity. We also support studies on the role of chronic infection in allergy-related and metabolic disease susceptibility. Building on recent findings, exploiting unique platforms that we have established, we aim to determine the effects of infectious exposures (prenatal, cumulative life-time and current, active exposures) on health outcomes comprising: 1. Vaccine immunogenicity 2. Infectious disease susceptibility – focussing on oncogenic viruses 3. Asthma phenotypes and allergy-related effector mechanisms 4. Infection, inflammation and cardio-metabolic risk To obtain deeper insights into mechanisms by which infections have their effects, we plan complementary studies (for which funding is available, or being sought elsewhere) on the mediating role of the microbiome and on the mediating role of epigenetic modifications In addition, the programme supports related studies on tuberculosis and schistosomiasis, and genetic studies.
2.1 Biological and endogenous factors / Unit