Restoration of BCG immunity after helminth induced epigenetic-mediated immune exhaustion
BACKGROUND: Helminth infection and TB are widespread with a quarter of the world at risk for helminth infection and over 10 million TB cases per year (resulting in 220,000 childhood TB deaths annually). Helminth infection results in persistent epigenetic-mediated inhibition of vaccine immunity in general, and specifically ablation of BCG immunity with an associated increased risk of developing TB.
GAP: TB vaccine research will be hindered if it fails to consider participants’ previous infections that imprint epigenetic marks that block the development of robust vaccine immunity.
HYPOTHESIS: My global hypothesis is that the host’s capacity to develop long-lived mycobacterial vaccine immunogenicity is epigenetically determined. Specifically, since helminth-infection imprints a long-lasting epigenetic-mediated immune exhaustion, it is critical to identify the ideal time during which a host is optimally receptive for BCG vaccination.
METHODS: BCG revaccination will be randomized to immediate, 2-months or 6-months after successful schistosomiasis therapy with vaccine immunogenicity determined 6-months post revaccination.
IMPACT: If BCG revaccination is able to reverse epigenetic-mediated immune exhaustion and restore immunogenicity, then targeted revaccination post deworming should improve clinical outcomes. If BCG is unable to restore immunity, then using Bioinformatics analysis, we will identify alternative means to reverse epigenetic immune exhaustion and restore vaccine immunity.