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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 6

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

A. The PENT (1∶540) for DENV4-immune human serum was determined in K562 cells. B. DENV4-immune human serum diluted 1∶540 was incubated with modified MAbs at 1,000 ng/mL. Relative infection was calculated as described in Figure 5. The data displayed are combined from five independent experiments, and the mean +/− SEM is displayed for each MAb. A sign rank test was used to determine whether relative infection with each modified MAb was significantly lower than relative infection of 0.5 (50% infection), * P<0.05, ** P<0.08. C. AG129 mice (n = 3 per experimental group and n = 6 for non-treated control group) were administered an enhancing dose of DENV4-immune human serum, infected with DENV2 D2S10, and 24 hours later treated with 20 µg of modified MAbs. A Kaplan-Meier survival curve is shown, and log-rank analysis was used for statistical comparison.

Figure 6