Discovery & validation of novel P. vivax antigens for identification and monitori

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DESCRIPTION (provided by applicant): As national malaria-control programs are intensifying and moving towards the goal of elimination, the primary focus has shifted from case management to the interruption of transmission. This will require the efficient and accurate identification of residual transmission foci that can be specifically targeted for elimination. Optimal surveillance systems should collect information on an ongoing basis to allow for a virtually real-time assessment of changes, while at the same time can be combined with other programmatic information to assist in planning, implementation, and modification/adjustment of malaria control activities to improve program performance. Whereas the current tools are not particularly suitable for this purpose, serological measurement, based on antibody prevalence, has been proposed as an alternative approach. Although this works well in areas of stable, low-level transmission, the vaccine antigens evaluated track changes in transmission very slowly and are thus of limited use in a rapidly changing environment where timely and actionable information is required. Thus there is an urgent need to identify a novel category of antigens with relatively short half-lives (6-8 weeks), and limited memory, for use in surveillance activitie. This need is particularly urgent for P. vivax, because well- characterized P. vivax candidate antigens are severely lacking. This study proposes to identify P. vivax proteins that can be used as antigens to screen for short half-life immune response, informing the recent history of parasite infection. Using multiplex bead assays, over 1,000 P. vivax proteins, produced by cell-free systems, will be screened against human plasma collected at different time intervals from P. vivax-infected subjects during clinical episodes and populations at risk in malaria endemic areas under a cohort epidemiological study with well-defined duration of new infection and post-treatment parasite clearance. The full kinetics profiles for antibodies to 100 selected antigens will be determined though analyzing the antibody titers at all time-points, to determine antibody half-lives. The 20 antigens with the best kinetic profiles (limited post-treatment antibody production, antibody half-life of 6-8 weeks, limited individual variation) will be selected for furher validation for use as surveillance candidate antigen to identify transmission hot-spots, using plasma from school-aged children in malaria-endemic and non-endemic areas. This study will result in the development of a novel serological assay to identify P. vivax transmission and its utility for detecting (residual) transmission 'hot-spots' among populations, and recent infections.