A Humanized Neutralizing Antibody Protects Against Human Adenovirus Type 7 Infection in Humanized Desmoglein-2 and CD46 Double-receptor Transgenic Mice

Overview

Journal Virol J

Publisher Biomed Central

Specialty Microbiology

Date 2024 Nov 16

PMID 39548554

Authors

Chengxing Zhou

Xiaohong Liao

Zhichao Zhou

Chuncong Mo

Yujie Yang

Hui Liao

Minglei Liu

Qiong Zhang

Qiuru Li

Xingui Tian

Rong Zhou

Hong Cao

Affiliations

Soon will be listed here.

Abstract

Background: Human adenovirus type 7 (HAdV7) has become a major public health threat due to its widespread transmission, severe associated pneumonia, and a lack of effective anti-HAdV7 drugs. The aim of the current study is to design a humanized monoclonal antibody (mAb) demonstrating efficacy against HAdV-7 infections in vitro and in vivo.

Methods: The humanized neutralizing antibody, 3G5-hu, was derived from the murine mAb 3G5. Antibody activity was evaluated using a flow cytometry-based neutralization (FCN) assay to identify humanized mAbs retaining potent neutralizing activity. Additionally, a humanized hDSG2/hCD46 dual-receptor transgenic mouse model was developed to simulate HAdV-7 infection.

Results: Using recombinant HAdV-7 expressing enhanced green fluorescent protein and clinically isolated wild-type HAdV-7, the half-maximal effective concentration of 3G5-hu against HAdV-7 was determined to be < 30 ng/mL. Notably, 3G5-hu exhibits high specificity for the hexon protein of the HAdV-7 capsid (affinity: KD = 9.02 × 10 M). Microneutralization studies with wild-type HAdV-7 and rAd7EGFP confirmed that humanized mAb 3G5-hu neutralizes 10-30 ng/mL HAdV-7 (approximately 67-200 pM). Furthermore, hDSG2/hCD46 double-receptor transgenic mice are more susceptible to HAdV-7 infection than single-receptor transgenic mice. Meanwhile, the humanized mAb 3G5-hu provides good protection against HAdV-7 infection in hDSG2/hCD46 knock-in transgenic mice.

Conclusions: The newly designed humanized mAb 3G5-hu specifically neutralizes HAdV-7 in vitro and in vivo. 3G5-hu elicits protection against HAdV-7 infection in hDSG2/hCD46 knock-in transgenic mice. The findings of this study provide insights to guide the future development of preventative and therapeutic treatments for HAdV-7 infection.

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