Development of Onchocerca volvulus in humanized NSG mice and detection of parasite biomarkers in urine and serum

Patton, John B.; Bennuru, Sasisekhar; Eberhard, Mark L.; Hess, Jessica A.; Torigian, April; Lustigman, Sara; Nutman, Thomas B.; Abraham, David

SGM, NRG and NSG (HuNSG) mice humanized with CD34 + umbilical cord derived stem cells were infected with 100 O. volvulus L3. Each of these humanized mice had human hematopoietic lineage cells at a concentration greater than 600 cells per μl of blood. While a complete picture of the cell populations in these specific mice was not determined, based upon flow analysis during the screening process all humanized mice had both human B and T-cells present in their blood. At 4-weeks post-infection humanized SGM mice contained a GM of 2.4 (range 1-7) worms/mouse, humanized NRG mice had a GM of 1.7 (range 1 to 4) worms/ Table) . HuNSG at 4-weeks post-infection had a 69% established infection rate with a GM of 3.4 (range 1-14) worms/mouse, and at 8-weeks post infection HuNSG mice had a 46% established infection rate and a GM of 2.6 (range 1-18) worms/mouse (Fig 1C) . Larval growth in HuNSG mice was comparable to that seen in NSG and in NSG mice engrafted with HuSkMc (Fig 2) . A significant increase in length was seen between the L3 and 4-week recovery 12 ). After 4-, 8-or 12-weeks the percent established (the proportion of mice in a group of infected animals from which live parasites were recovered) (Fig 1A-1D ) and the geometric mean number of live worms recovered per mouse within the group was determined (Fig 1E-1H) .