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.

to death. It has been demonstrated that prophylactic administration of human purified polyvalent immunoglobulins G (IgG) containing anti-CHIKV antibodies (CHIKVIGs) protected susceptible IFNα/βR−/− adult animals and wild-type neonates during CHIKV infection 49 . To assess if these antibodies could exacerbate CHIKV disease severity at sub-neutralizing concentrations, different concentrations of CHIKVIGs were administered intra-peritoneally to CHIKV-infected 11 days old C57BL/6 WT mice at the ventral thorax 40 (Fig. 7) . Mortality was observed in mice receiving CHIKVIGs at concentrations of 1-100 µg/kg (Fig. 7a) , whereas mice receiving either 1000 µg/kg or 0.1 µg/kg of CHIKVIGs survived the infection. Unexpectedly, approximately 30% of mice receiving a control non-CHIKV-specific polyvalent IgG also died from infection (Fig. 7a) . Nevertheless, viral RNA load in serum, liver and muscles was determined in CHIKV-infected mice receiving 10 µg/kg of CHIKVIGs. It was observed that enhanced CHIKV infection led to a more significant viral burden in the muscles at 3 dpi ( Fig. 7b) , but not at 6 dpi (Fig. 7c) . Taken together, these findings highlight that enhanced CHIKV infection is detrimental in young animals.