Immunome Research
Open Access
ISSN: 1745-7580
+44-77-2385-9429
ISSN: 1745-7580
+44-77-2385-9429
Thomas S Watkins, Fiona Amante, Steve Turner, Amy Ransier, Daniel C Douek, Denise L Doolan, James S McCarthy and John J Miles
AITHM - James Cook University, Australia
Scientific Tracks Abstracts: Immunome Res
Malaria infection still remains one of the worldâ??s most formidable issues across both health and economical systems. Despite the best intervention strategies over 200 million people are infected annually, and mortality rates exceed 400,000 deaths per year. To develop effective therapeutics and vaccines a better understanding of fundamental human immunology is required. This is particularly true of the contribution of T cells to malaria defence. Research to date comes from field samples which can sometimes be difficult to interpret due to confounding factors including multiple exposures. As such, the underlying immune correlates of an efficient response remain unknown. To investigate the role of T cells in disease we used a human model of blood stage Plasmodium falciparum infection involving the medicines for malaria venture (MMV). We performed high-dimensional phenotyping and T cell receptor (TCR) sequencing of T cell subsets before infection, during infection and during convalescence. Plasmodium falciparum infection resulted in marked phenotypic scaring across all T cell subsets and persisted during convalescence. We identified gene modules that correlated with parasitaemia, revealing possible continua between individuals at risk of disease and elite controllers. Remodelling of the TCR repertoire could also be correlated with transcriptomic changes, and gene expression and TCR repertoire metrics could serve as novel proxies of disease burden and assist in identifying pathways for immunotherapies or vaccine activation. Indeed, characterizing the T cell biology of elite controllers opens the possibility of inducing this phenotype for the purposes of rational vaccine design and therapeutic intervention.
Thomas S Watkins has completed his undergraduate degree at Cardiff University, where he worked at the Institute of Infection and Immunity in the lab of Professor David Price. He is now a PhD student at the Australian Institute of Tropical Health and Medicine, located at James Cook University in Cairns, Australia. His research focuses on the analysis of T cell receptor repertoires in health and disease.
E-mail: thomas.watkins@my.jcu.edu.au