MVI is expanding on previous efforts that investigated assays for measuring the functional anti-parasitic activity of antibodies. The aim is to go beyond looking at functional assays for circumsporozoite (CSP) antibodies, with the goal of using such assays for other pre-erythrocytic antigens. A number of approaches toward development of novel assays and optimization of existing ones are being undertaken, and down-selection to a smaller number of assays is planned based on criteria such as correlation with mouse models, protection in clinical trials, throughput, and cost. MVI is supporting a portfolio of projects aimed at several objectives, including improvements on existing assays, development of novel assays (particularly those that detect Fc effector function), and generation of reference reagents. In assay improvement projects, work in this category is aimed at reducing background and variability, increasing throughput, and automating readouts. We are collaborating with several groups that are developing assays aimed at assessing the role of Fc effector function, such as sporozoite opsonization and complement fixation, as well as the extent to which Fc effector function contributes to inhibitory activity observed in the functional assays. Other projects are focused on generating anti-sporozoite monoclonal antibodies that can be used as standards for functional assays as well as a stable long term source of hepatocytes.
Zou X, House BL, Zyzak MD, Richie TL, Gerbasi VR. Towards an optimized inhibition of liver stage development assay (ILSDA) for Plasmodium falciparum. Malar J. 2013 Nov 5;12:394. doi: 10.1186/1475-2875-12-394.
Kaushansky A, Rezakhani N, Mann H, Kappe SH. Development of a quantitative flow cytometry-based assay to assess infection by Plasmodium falciparum sporozoites. Mol Biochem Parasitol. 2012 May;183(1):100-3. doi: 10.1016/j.molbiopara.2012.01.006. Epub 2012 Feb 8.