The gut microbiome in vaccine-specific immune responses among rural and urban Ugandan adolescents

PROJECT OVERVIEW

Few public health interventions have had as profound an effect on global health as vaccination; however, not all individuals benefit equally from existing vaccines. Previous studies have shown variability in vaccine efficacy and vaccine-specific immune responses between populations. For example, BCG-induced protection against pulmonary tuberculosis (TB) ranges from zero in sub-Saharan Africa to 80% in the global north (Fine 1995), and the antibody response to the yellow fever vaccine is lower in Ugandans compared to Swiss volunteers (Muyanja et al., 2014).

The biological basis of individual and population differences in vaccine response is incompletely understood. While host genetic and environmental factors likely play a key role, the composition of the human gut microbiome may also be important, particularly through its ability to modulate the host immune system (Lynn et al. 2022).

This project will take advantage of three inter-related vaccine trials in rural and urban settings in Uganda (Population Differences in Vaccine Responses, POPVAC, Nkurunungi et al. 2021). In doing so, it will seek to understand how the gut microbiome is modulated by host and environmental factors (immune status, parasitic infection, nutritional status), before going on to identify links between the composition of the gut microbiome and responses to live parenteral (BCG, yellow fever), live oral (typhoid), virus-like particle (Human Papillomavirus) and toxoid (Tetanus/Diphtheria) vaccines.

This opportunity would suit someone with a direct interest in the microbiome and its contribution to immunological factors influencing vaccination against infectious diseases that remain prevalent in sub-Saharan Africa. Applicants should be eligible for funding via the Africa Oxford Initiative (AfOx) Kennedy Trust Prize Studentship.

TRAINING OPPORTUNITIES

This position represents a collaboration between the Oxford Centre for Microbiome Studies at the Kennedy Institute for Rheumatology and the Medical Research Council/Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine Uganda Research Unit.

The successful applicant will gain experience of working as part of the established POPVAC trial team. They will also receive complementary laboratory and bioinformatic training necessary for the generation and handling of microbiome data and the integration of such data with trial results. They will be expected to publish results in peer-reviewed journals and present at national and international scientific conferences.

As well as institutional support, the successful applicant will benefit from being part of the University of Oxford college system and the Africa Oxford Initiative.

KEY PUBLICATIONS

1. Nkurunungi G. et al. (2021) http://dx.doi.org/10.1136/bmjopen-2020-040425
2. Fine P.E.M. (1995) https://doi.org/10.1016/S0140-6736(95)92348-9
3. Muyanja E. et al. (2014) https://doi.org/10.1172/JCI75429
4. Lynn D. J. et al (2022) https://doi.org/10.1038/s41577-021-00554-

KEY THEMES

Microbiome-immune interactions
Population differences in vaccine response
Helminth infection
Metagenomics

KEYWORDS

Microbiome, Vaccination, Helminth Infection, BCG