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

Area of Science:

• Immunology
• Virology
• Biotechnology

Background:

• West Nile fever, caused by West Nile virus (WNV), poses a significant public health risk.
• Current treatment options for WNV infection are limited, highlighting the need for novel therapeutic strategies.

Purpose of the Study:

• To develop and evaluate a novel recombinant chimeric monoclonal antibody (mAb) for WNV treatment.
• To assess the efficacy of the engineered mAb 900 in preclinical models.

Main Methods:

• Generation of a chimeric mAb (mAb 900) by fusing murine antibody 9E2 antigen-binding regions with human IgG1 constant domains.
• Engineering mAb 900 with specific amino acid substitutions to enhance neonatal Fc receptor (FcRn) binding.
• Production and purification of mAb 900 in CHO cells, followed by biophysical characterization.
• Evaluation of antigen-binding affinity, virus-neutralizing activity, and protective efficacy in a lethal mouse model of WNV infection.

Main Results:

• Engineered mAb 900 demonstrated high homogeneity, stability, and correct dimeric assembly.
• mAb 900 retained the potent virus-neutralizing activity and high antigen-binding affinity of its murine precursor.
• Significant protective efficacy was observed in a lethal mouse model of WNV infection, establishing proof of concept.

Conclusions:

• The engineered chimeric mAb 900 is a promising therapeutic candidate for West Nile virus infection.
• Further preclinical development of mAb 900 is warranted based on its demonstrated efficacy and safety profile.