Fig. 3: Antibody dependent enhancement of YF17D virus infection mediated by TBEV vaccine-induced IgG.

A Flow cytometric determination of venus-YF17D virus infection of THP-1 cells in the absence or presence of cross-reactive serum from a TBEV-vaccinated individual. The conditions tested include polyclonal serum alone or in combination with FcγR-blocking antibodies and IgM or IgG-depleted serum. B ADE of YF17D mediated by study participants’ serum (n = 132 TBEV-vaccinated, n = 53 TBEV-unvaccinated individuals). Virus infection was quantified in combination with serially diluted serum and was normalized against the enhancement of a 1:20 diluted enhancing-serum control carried for all measurements. Thick dashed line indicates the mean of the different just-virus controls and dotted lines define +/− 1 SD. The curve was fitted with local regression with a 0.95 confidence interval. C Quantification of the enhancing titer as AUC of the normalized virus infection across serial dilutions shown in B. D Comparison of anti-YF17D-DIII specific IgG titer at day 28 post-vaccination for both TBEV groups (n = 36 TBEV-unvaccinated, n = 117 TBEV-vaccinated individuals). Longitudinal quantification of anti-YF17D-DIII (E, n = 97 donors) and anti-TBEV-DIII (F, n = 114 donors) specific IgG in TBEV-experienced individuals. G Paired comparison of the DIII-specific IgG fold-change between day 28 and day 0 for TBEV and YF17D (n = 76 pairs). H Spearman correlation in TBEV-experienced individuals of baseline anti-E IgG and enhancing titers versus YF17D vaccine-induced neutralizing antibody titer at day 28, anti-sE and anti-DIII IgG titers and baseline anti-YF17D-E and anti-YF17D-DIII IgG titers. Color intensity reflects the Spearman correlation coefficient. I Comparison of the first (n = 34) and fourth (n = 33) quartile group of YF17D-sE specific IgG at baseline and the anti-YFDIII IgG on baseline and day 28, the anti-YF17D-sE IgG titer on day 28 and the anti-YF17D neutralizing antibody titer on day 28 (high vs. low quartile n = 24/23, 32/28, 33/32, 34/33 respectively). J Comparison of the first (n = 33) and fourth (n = 33) quartile group of the Enhancing titers at baseline and the anti-YFDIII IgG on baseline and day 28, the anti-YF17D-sE IgG titer at baseline and day 28 and the anti-YF17D neutralizing antibody titer on day 28 (high vs low quartile n = 25/22, 28/30, 32/33, 32/33, 33/33, respectively). TBEV-vaccinated participants are depicted in orange and TBEV-unvaccinated in blue. Boxplots show a horizontal line indicating the median and lower and upper hinges corresponding to the first and third quartiles. The lower and upper whiskers extend to 1.5x IQR from the respective hinge. Statistical significance between TBEV-vaccinated and unvaccinated individuals (D) and between high and low quartiles (I, J) is shown above every comparison and was estimated with a two-sided Mann-Whitney test. Statistical significance in E–G was calculated with a two-sided Wilcoxon signed-rank test. P values above 0.05 are considered non-significant (ns).