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

Content Provider	Springer Nature : BioMed Central
Author	Zhou, Chengxing Liao, Xiaohong Zhou, Zhichao Mo, Chuncong Yang, Yujie Liao, Hui Liu, Minglei Zhang, Qiong Li, Qiuru Tian, Xingui Zhou, Rong Cao, Hong
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.
Related Links	https://virologyj.biomedcentral.com/counter/pdf/10.1186/s12985-024-02572-y.pdf
Ending Page	15
Page Count	15
Starting Page	1
File Format	HTM / HTML
DOI	10.1186/s12985-024-02572-y
Journal	Virology Journal
Issue Number	1
Volume Number	21
Language	English
Publisher	BioMed Central
Publisher Date	2024-11-16
Access Restriction	Open
Subject Keyword	Virology Human adenovirus type 7 Neutralizing monoclonal antibodies Receptors Transgenic mice Humanized antibodies
Content Type	Text
Resource Type	Article
Subject	Virology Infectious Diseases
Journal Impact Factor	4/2023
5-Year Journal Impact Factor	3.8/2023

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