Antibody-mediated enhancement aggravates chikungunya virus infection and disease severity

Lum, Fok-Moon; Couderc, Thérèse; Chia, Bing-Shao; Ong, Ruo-Yan; Her, Zhisheng; Chow, Angela; Leo, Yee-Sin; Kam, Yiu-Wing; Rénia, Laurent; Lecuit, Marc; Ng, Lisa F. P.

Healthcare Group with Domain Specific Review Board no. DSRE E/08/414. Written informed consent was obtained from all CHIKF patients prior to the collection of samples. Human blood samples were obtained from healthy donors with written informed consent in accordance with the guidelines from the Health Sciences Authority of Singapore (study approval number: NUS IRB number 10-250). Animal studies protocols were Figure 6 . Aggravated disease outcome in CHIKV-infected IFNαR+/− mice. Three-weeks old IFNαR+/− female mice (n = 7 to 11 animals per group) were infected via footpad inoculation with 10 6 PFU of CHIKV. Immediately, these mice were administered intraperitoneally with ~2 µg/ml (total IgG concentration) mice sera from CHIKV-infected mice (enhanced) or PBS (non-enhanced). Daily assessment of (a) viremia and (b) disease score were performed. Data are presented as mean ± SD by Mann-Whitney U test (**P = 0.0027, **P = 0.0011, ***P = 0.0009, ***P = 0.0005, **P = 0.0017 and *P = 0.0159 for 2, 3, 4, 5, 6 and 7 dpi viremia respectively; + P = 0.0125, +++ P < 0.0001, ++ P = 0.0015 and + P = 0.0277 for 4, 5, 6 and 7 dpi viremia respectively; *P = 0.0109 and *P = 0.0306 for 10 and 11 dpi disease score respectively; +++ P < 0.0001, +++ P = 0.0006, + P = 0.0109, + P = 0.0277, + P = 0.0031, + P = 0.0095 and + P = 0.0031 for 1, 6, 7, 8, 9, 10 and 11 dpi disease score respectively. (*) indicates significance comparing between CHIKV-infected IFNαR+/− (blue) and WT animals (black); (+) indicates significance comparing between IFNαR+/− mice infected under enhanced (red) and non-enhanced (blue) conditions. 8, 9, 35 were used in this study. These plasma have previously been characterized 44, 61, 62, 66 . In this study, plasma samples collected 2-3 months post-illness onsets were used. All patient plasma were aliquoted and stored at −80 °C. Plasma samples were also collected from 8 healthy volunteers as controls.