P005 Cellular responses to repeated malaria episodes: Does the concept of original antigenic sin apply to Plasmodium falciparum malaria?

Introduction Despite the marked reduction in reported cases of P. falciparum malaria, this disease remains a major global health threat claiming the lives of 655,000 people and putting an estimated 3.3 billion of the world’s population at risk of illness. Although people living in malaria-endemic areas mount a broad range of immune responses to a great variety of parasite antigens, protective immunity to clinical malaria develops only slowly, and some argue the duration of such responses is comparatively short-lived. The concept of original antigenic sin, whereby an initial infection imprints a certain response pattern that prevents the immune system from mounting more efficient responses upon subsequent infections, may explain these observations. Methods In a longitudinal cohort study of Malian children aged 0.5 to 10 years, we investigate whether a child experiencing repeated malaria episodes mounts similar immunological responses each time. We also investigated whether these responses can be grouped into distinct patterns, and whether any distinct patterns associate with disease outcome. Results We are currently characterizing the quality and magnitude of parasite antigen-specific T cell responses after in vitro stimulation of peripheral blood mononuclear cells collected during an acute malaria episode using multi-parameter flow cytometry. Based on cell surface phenotype we classify memory CD4 + and CD8 + T cells into effector memory (CD45RO + CCR7 − ) and central memory (CD45RO + CCR7 + ) T cells and characterize their function by measuring the production of IFN ϒ , TNF α , IL-2 and IL-10. We also quantify cytokine levels in the corresponding supernatants and plasma samples using multi-parameter Bioplex assays. Conclusion The results of this study will enable us to determine whether original antigenic sin influences malaria incidence, and may reveal an association between a specific immunological response pattern and enhanced protection from a subsequent malaria episode, which can be further explored in identifying candidate vaccine antigens.