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

NSG mice were infected with 100 O. volvulus L3 and necropsied at 4-and 8-weeks following infection. Infected mice had an established infection rate of 63% with a GM worm recovery of 2.0 (range 1 to 4) worms recovered at 4-weeks following infection. At 8-weeks, 75% of mice had an established infection, with a GM recovery of 1.4 (range 1 to 3) worms per mouse ( Fig 1A) . The recovered worms were measured and found to be significantly increased in size (p<0.0001; Min: 677 μm, Max 843 μm, GM: 717 μm) at 4-weeks compared to L3. They also significantly increased in size between 4 and 8 weeks (p<0.0001) reaching a maximum of 1,085 μm (Min: 700 μm, GM: 1034 μm) (Fig 2) . Table) . Mice engrafted with LEC had 20% established infection and GM of 4 worms recovered per mouse with a range of 1 to 4 worms per mouse (S1 Table) . HaCaT cell engrafted mice had a 60% established infection and GM recovery 1.7 worms recovered per mouse with between 1 and 2 worms per mouse (S1 Table) . HuSkMc cell engrafted mice had an 81% estab- (Fig 1B) . At each time point tested the parasites in HuSkMc-engrafted mice demonstrated continued parasite growth. At 4-weeks recovered parasites had GM lengths of 713 μm (Min: 592 μm, Max: 788 μm), at 8-weeks lengths of 751 μm (Min: 642 μm, Max: 1,081 μm), and at 12-weeks the GM length was 1,121 μm with a maximum length of 2,086 μm observed (Min: 748 μm), representing a 4-fold increase in length over L3 (Fig 2) . These growth rates represented significant changes between L3 and 4-week worms (p = 0.0010) and between 8-and 12-week worms (p<0.0001).