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Detection of Neutralization-sensitive Epitopes in Antigens Displayed on Virus-Like Particle VLP-Based Vaccines Using a Capture Assay
Published on: February 10, 2022
Identification of four neutralizing antigenic sites on the enterovirus D68 capsid
Wenlong Dai1, Xue Li2,3, Zeyu Liu3
1Department of Pharmaceutics, National Vaccine Innovation Platform, School of Pharmacy, Nanjing Medical University, Nanjing, China.
Importance:
Enterovirus D68 (EV-D68) is an emerging respiratory pathogen associated with acute flaccid myelitis. Currently, no approved vaccines or antiviral drugs are available. Here, we report four functionally independent neutralizing antigenic sites (I to IV) by analyses of neutralizing monoclonal antibody (MAb)-resistant mutants. Site I is located in the VP1 BC loop near the fivefold axis. Site II resides in the VP2 EF loop, and site III is situated in VP1 C-terminus; both sites are located at the south rim of the canyon. Site IV is composed of residue in VP2 βB strand and residues in the VP3 BC loop and resides around the threefold axis. The developed MAbs targeting the antigenic sites can inhibit viral binding to cells. These findings advance the understanding of the recognition of EV-D68 by neutralizing antibodies and viral evolution and immune escape and also have important implications for the development of novel EV-D68 vaccines.
Insights
Researchers identified four key sites on Enterovirus D68 (EV-D68) that antibodies target to neutralize the virus. This discovery is crucial for developing new EV-D68 vaccines and antiviral therapies.
Area of Science:
- Virology
- Immunology
- Vaccine Development
Background:
- Enterovirus D68 (EV-D68) is an emerging respiratory pathogen linked to acute flaccid myelitis.
- There are currently no approved vaccines or antiviral treatments for EV-D68 infections.
Purpose of the Study:
- To identify and characterize neutralizing antigenic sites on EV-D68.
- To provide insights for the development of novel EV-D68 vaccines and therapeutics.
Main Methods:
- Analysis of neutralizing monoclonal antibody (MAb)-resistant mutants.
- Mapping of antigenic sites to specific viral protein regions.
Main Results:
- Four functionally independent neutralizing antigenic sites (I to IV) were identified on EV-D68.
- Site I is in the VP1 BC loop, Site II in the VP2 EF loop, Site III at the VP1 C-terminus, and Site IV involves VP2 and VP3 residues.
- Developed MAbs targeting these sites inhibited viral binding to cells.
Conclusions:
- These findings enhance understanding of EV-D68 antibody recognition, viral evolution, and immune escape.
- The identified antigenic sites are critical targets for future EV-D68 vaccine design.
