Real life immunology : environmental factors shape the immune system and vaccine responsiveness

Prevention of infectious diseases through vaccination is one of the greatest achievements of medicine, yet there is growing realisation that vaccine immunogenicity and efficacy varies greatly across populations in high- versus low/middle- income countries (LMIC) and in urban- versus rural areas within one country. For example, whereas vaccination of volunteers in Europe with attenuated malaria vaccine can result in 100% protection, the efficacy drops to only 29% when tested in parts of Africa, where it is needed most. Other vaccines, such as rotavirus, BCG, yellow fever and Ebola show similar trends in either immunogenicity or efficacy. In parallel, using technologies for in depth characterization of the immune system, strong variation in immunological profiles and function across geographical areas has been documented, influenced by non-heritable factors. We find that differences in cellular metabolism, expansion of cells with a highly activated footprint, increased regulatory cell frequencies, and skewing towards Th2, characterize the immune profiles of populations residing in rural areas of LMIC; areas where vaccine performance is poor. Identification of immunological pathways and response to perturbations in different environmental setting is needed to understand underlying mechanisms and improve vaccine responses. Through high dimensional immunological analyses of the immune system of human cohorts as well as controlled human infections and vaccination trials conducted in  different geographical areas, we are investigating how distinct immunological set points that are driven by environmental exposures, influence immune responsiveness. This can help us to identify modulators that can improve vaccine induced immunity in particular in those living in rural areas of LMIC.