Related Experiment Video
Updated: May 10, 2026
Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
Published on: March 2, 2014
Structurally conserved human anti-A35 antibodies protect mice and macaques from mpox virus infection
Bin Ju1, Congcong Liu2, Jingjing Zhang3
1Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong Province 518112, China; Guangdong Key Laboratory for Anti-infection Drug Quality Evaluation, Shenzhen, Guangdong Province 518112, China.
Abstract:
The A35 protein, expressed on the enveloped virion of monkeypox (mpox) virus (MPXV), is essential for viral infection and spread within the host, making it an effective antiviral target. In this study, we demonstrated two human anti-A35 monoclonal antibodies (mAbs) displayed potential protection against MPXV in CAST/EiJ mice and rhesus macaques. Using cryo-electron microscopy, we determined two high-resolution structures of the A35 dimer in complex with the fragment of antigen binding of mAb 975 or mAb 981, revealing detailed interactions at the antigen-antibody interfaces. Structural analysis showed that these structurally conserved mAbs bind to a groove region at the interface of A35 dimer. Overall, we provided a proof of concept for a single administration of anti-A35 mAbs mitigating the pathogenic effects of MPXV infection in rhesus macaques. These human-derived mAbs could be served as antibody drug candidates, and their binding models to the A35 dimer will provide valuable insights for future vaccine design.
Insights
Two human monoclonal antibodies (mAbs) show protection against monkeypox virus (mpox) infection. Structural analysis reveals how these anti-A35 mAbs bind the virus, offering insights for new antiviral therapies and vaccine design.
Area of Science:
- Virology
- Immunology
- Structural Biology
Background:
- The A35 protein on the monkeypox virus (mpox) virion is crucial for infection and spread.
- A35 presents a potential target for antiviral interventions.
Purpose of the Study:
- To evaluate the protective potential of human anti-A35 monoclonal antibodies (mAbs) against monkeypox virus (mpox) infection.
- To elucidate the structural basis of anti-A35 mAb binding to the A35 protein.
Main Methods:
- In vivo efficacy studies in CAST/EiJ mice and rhesus macaques.
- Cryo-electron microscopy to determine high-resolution structures of A35-mAb complexes.
- Detailed analysis of antigen-antibody interface interactions.
Main Results:
- Two human anti-A35 mAbs demonstrated protective effects against MPXV in animal models.
- Cryo-EM structures revealed conserved binding of mAbs to a groove at the A35 dimer interface.
- A single dose of anti-A35 mAbs mitigated MPXV infection in rhesus macaques.
Conclusions:
- Human anti-A35 mAbs are promising candidates for antibody-based mpox therapies.
- Structural insights facilitate the development of novel vaccines and therapeutics targeting MPXV.
- This study provides a proof of concept for anti-A35 mAb efficacy in mitigating mpox pathogenesis.
More Related Videos
13:14Generation of Discriminative Human Monoclonal Antibodies from Rare Antigen-specific B Cells Circulating in Blood
Published on: February 6, 2018
05:15Detection of Neutralization-sensitive Epitopes in Antigens Displayed on Virus-Like Particle VLP-Based Vaccines Using a Capture Assay
Published on: February 10, 2022
