Humanization and characterization of a murine monoclonal neutralizing antibody against human adenovirus 7.

ABSTRACT

Human adenovirus type 7 (HAdV7) is commonly associated with febrile acute respiratory disease (ARD) outbreaks. We have reported that 10G12, a mouse monoclonal antibody (mAb) specifically recognizing and neutralizing HAdV7, is a promising candidate for humanization. In this study, we engineered the six variants of 10G12 with increased degree of humanization and investigated their biological activity. The humanized monoclonal antibody (mAb) 10G12-M2 was shown to retain the parental antibody's high binding affinity, specificity and potent efficacy of viral suppression. The mAb 10G12-M2 recognized a conformational neutralization epitope of the hexon protein. Complex structure-based molecular docking simulation showed that the hexon protein formed several interactions with 10G12-M2, including hydrogen bonds and salt bridges interaction. Physicochemical properties analysis of 10G12-M2 demonstrated that it is stable and desirable lead candidate. In general, 10G12-M2 had excellent biological activity after humanization combined with the potential for use in prophylactic or therapeutic applications against HAdV7.