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Open Access 01-12-2024 | Research

A humanized neutralizing antibody protects against human adenovirus type 7 infection in humanized desmoglein-2 and CD46 double-receptor transgenic mice

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

Published in: Virology Journal | Issue 1/2024

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^− 11 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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Title: A humanized neutralizing antibody protects against human adenovirus type 7 infection in humanized desmoglein-2 and CD46 double-receptor transgenic mice
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
Publication date: 01-12-2024
Publisher: BioMed Central
Published in: Virology Journal / Issue 1/2024
Electronic ISSN: 1743-422X
DOI: https://doi.org/10.1186/s12985-024-02572-y

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