Does the Chimerization Process Affect the Immunochemical Properties of WNV-Neutralizing Antibody 900?

West Nile fever is an infectious disease caused by the West Nile virus (WNV), which is transmitted by mosquitoes. Epidemiological surveillance confirms the potential risk of WNV infection in human populations. The lack of specific antiviral therapeutics and vaccines against WNV underscores the urgent need to develop effective therapeutic approaches. In this study, a recombinant chimeric monoclonal antibody (mAb) 900 was generated based on the broadly neutralizing and protective murine mAb 9E2. The antigen-binding regions of the murine mAb were fused with the constant domains (CH2-CH3) of human IgG1. Two key amino acid clusters, M252/S254/T256 and H433/N434, were introduced into the CH2-CH3 domains to enhance the affinity of mAb 900 for the neonatal Fc receptor (FcRn). The engineered mAb 900 was produced in CHO cells and purified to high homogeneity. Biophysical characterization confirmed its stability and correct dimeric assembly. Comparative analysis demonstrated that mAb 900 retained the high antigen-binding affinity and potent virus-neutralizing activity of its murine predecessor. Most importantly, mAb 900 demonstrated significant protective efficacy in a lethal mouse model of WNV infection. These results establish the proof of concept for mAb 900 as a promising candidate for further preclinical development against WNV infection.