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. 2020 Sep 16;60:102991. doi: 10.1016/j.ebiom.2020.102991

Fig. 2.

Fig. 2:

Analysis of the capacity of anti-DSV4, anti-Dengvaxia and anti-TV DENV immune sera to enhance DENV infection in vitro and in vivo. (a–d) The graphs depict infection profiles of K562 cells by DENV-1 (squares), DENV-2 (circles), DENV-3 (triangles) and DENV-4 (diamonds) as a function of dilution of mock- (grey curves, panel ‘a’), α-DSV4- (orange curves, panel ‘b’), α-Dengvaxia- (blue curves, panel ‘c’) and α-TV DENV (purple curves, panel ‘d’) immune sera (raised in BALB/c mice), determined by flow cytometry. (e-h) Groups of AG129 mice (n=5) were administered either mAb 4G2 (grey curves), mock- (green curves), DSV4- (orange curves), Dengvaxia- (blue curves) or TV DENV- (purple curves) immune sera by passive transfer (10 µg mAb or 20 µl immune serum in a final volume of 200 µl 1x PBS), then challenged with a sub-lethal dose of DENV-2 S221 (panel ‘e’) and monitored for survival (panel ‘f’), clinical signs (panel ‘g’) and body weight change (panel ‘h’) over the next 15 days. A group of mice which received no treatment (Uninfected, black curves) was monitored in parallel for comparison. Survival data (in panel ‘f’) were analysed by Log-Rank (Mantel-Cox) test for significant difference in survival rates. Survival of mice which received either mock immune serum or α-DSV4 before challenge was not significantly different from that of Uninfected mice (100% survival). In comparison, survival was significantly reduced (p<0.05) in mice which received α-Dengvaxia immune serum and very significantly reduced (p<0.002) in mice which received α-TV DENV immune serum or mAb 4G2. In panel ‘g’, clinical scores were based on a 5 point system, with the maximum score denoting death: 0.5, mild ruffled fur; 1.0, ruffled fur; 1.5, compromised eyes; 2, compromised eyes with hunched back; 2.5, loose stools; 3.0, limited movement; 3.5, no movement/hind leg paralysis; 4.0, euthanised if cumulative score was 5. In panel ‘h’, body weight was monitored twice a day in the morning and evening, and the mean taken for plotting. Note: in panels ‘e-h’ a second pool of anti-Dengvaxia immune serum (α-Dengvaxia-CD11c+DENV-2 S221, dashed blue curves), raised by immunising CD11c-Ifnar1−/− mice, was also tested (all other murine immune sera are from BALB/c mice) (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article).