Modulating Chikungunya and Mayaro virus-induced disease severity in mice using low concentrations of anti-IFNAR1 antibodies.

Abstract

The laboratory mouse () is the most widely used animal model for preclinical research, with numerous wild-type and genetically modified mouse strains available. Chikungunya virus (CHIKV), a mosquito-borne arthritogenic alphavirus, has emerged in various new regions and caused several millions of cases within the last decade. Mayaro virus (MAYV), an arthritogenic alphaviruses closely related to CHIKV, remains geographically restricted to the Americas. Existing mouse models rely on immunodeficient mice, leading to lethal illness, or footpad injection, which induces localized arthropathy. We present a proof-of-concept study demonstrating how disease severity in mice can be modulated using sub-neutralizing concentrations of an interferon 1 receptor (IFNAR1) blocking monoclonal antibody (mAb). C57BL/6 mice were injected intraperitoneally with varying anti-IFNAR1 antibody doses before intraperitoneal infection with CHIKV or MAYV. For both, CHIKV and MAYV, we observed an anti-IFNAR1 mAb dose-dependent increase in blood viral loads and disease severity. A 1mg dose induced severe disease, whereas a 0.1 mg dose resulted in moderate symptoms in mice, mainly facial pain expression signs, accompanied by detectable viremia in the days preceding symptom onset. Viral loads in organs and serum concentrations of inflammatory cytokines and chemokines were also elevated in mice receiving 0.1mg anti-IFNAR1 mAb. In conclusion, we provide proof of concept that CHIKV and MAYV disease severity can be modulated using low concentrations of anti-IFNAR1 mAb. We used this approach to develop a new infection model for mild systemic disease, based on an accessible strain and a commercial antibody allowing for easy implementation and adaptation.