Recombinant Human Anti-E protein Antibody (E76)

A. Ribbon diagram of the DENV2 E protein homodimer (PDB ID code 1OAN). EDI is red, EDII is yellow and EDIII is blue. The epitopes targeted by MAbs include the fusion loop (green), dimer interface (white), C-C′ loop (orange) and A strand (magenta). B. AG129 mice were administered a lethal dose of DENV2 D2S10 and 24 hours later were treated with 20 µg of modified MAbs (n = 5 per group from 2 independent experiments). C. AG129 mice were administered an enhancing dose of polyvalent DENV1-immune mouse serum, infected with DENV2 D2S10, and 24 hours later treated with 20 µg of modified MAbs. (n = 3–19 per group from at least 2 independent experiments for each modified MAb). A Kaplan-Meier survival curve is shown (B–C), and log-rank analysis was used for statistical comparison.

Williams, K. L., Sukupolvi-Petty, S., Beltramello, M., Johnson, S., Sallusto, F., Lanzavecchia, A., ... & Harris, E. (2013). Therapeutic efficacy of antibodies lacking FcγR against lethal dengue virus infection is due to neutralizing potency and blocking of enhancing antibodies. PLoS pathogens, 9(2), e1003157.

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).

Williams, K. L., Sukupolvi-Petty, S., Beltramello, M., Johnson, S., Sallusto, F., Lanzavecchia, A., ... & Harris, E. (2013). Therapeutic efficacy of antibodies lacking FcγR against lethal dengue virus infection is due to neutralizing potency and blocking of enhancing antibodies. PLoS pathogens, 9(2), e1003157.

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. 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.

Williams, K. L., Sukupolvi-Petty, S., Beltramello, M., Johnson, S., Sallusto, F., Lanzavecchia, A., ... & Harris, E. (2013). Therapeutic efficacy of antibodies lacking FcγR against lethal dengue virus infection is due to neutralizing potency and blocking of enhancing antibodies. PLoS pathogens, 9(2), e1003157.