Rapid In Vivo Screening of Monoclonal Antibody Cocktails Using Hydrodynamic Delivery of DNA-Encoded Modified Antibodies

<b>Background:</b> Monoclonal antibodies (mAbs) are potent treatment options for infectious diseases. The rapid isolation and in vivo validation of therapeutic mAb candidates, including mAb cocktails, are essential to combat novel or rapidly mutating pathogens. The rapid selection and production of mAb candidates in sufficient amount and quality for preclinical studies are a major limiting step in the mAb development pipeline. <b>Methods:</b> Here, we developed a method to facilitate the screening of therapeutic mAbs in mouse models. Four conventional mAbs were transformed into single-chain variable fragments fused to the fragment crystallizable (Fc) region of a human IgG1 (scFv-IgG). These scFv-IgG were expressed individually or as a cocktail in vitro and in mice following transfection or hydrodynamic delivery of the corresponding plasmids. <b>Results:</b> This method induced high expression of all scFv-IgG and provided protection in two murine infection models. <b>Conclusions:</b> This study highlights the benefits of this approach for the rapid, low-cost screening of therapeutic mAb candidates.