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Therapeutic Efficacy of Antibodies Lacking FcγR against Lethal Dengue Virus Infection Is Due to Neutralizing Potency and Blocking of Enhancing Antibodies

Figure 5

In vitro suppression-of-enhancement assay predicts therapeutic efficacy of MAbs in vivo with enhancing polyvalent DENV-immune serum from mice.

A. The peak enhancing titer (PENT = 1∶180) for DENV1-immune mouse serum was determined in K562 cells. B. DENV1-immune mouse serum was diluted 1∶180 (PENT) and incubated with modified MAbs at six 2-fold dilutions beginning at 2,000 ng/mL. Relative infection was calculated by dividing the percent infection in the presence of modified MAbs by the percent infection measured with mouse DENV1-immune serum alone. The data displayed are the average of duplicate values and are representative of four independent experiments. A † indicates modified MAbs that are statistically therapeutic in vivo following mouse DENV1-enhanced, lethal DENV2 infection. C. The average infection across four experiments at 1,000 ng/mL of modified MAb (mean +/− SEM shown for each MAb). P<0.04 was obtained when comparing the average relative infection values for therapeutic to non-therapeutic MAbs using a Wilcoxon rank-sum analysis. The solid line indicates relative infection of 0.5 (50% infection).

Figure 5