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Updated: Jun 15, 2026
Author Spotlight: Advancing Antiviral Strategies Through Novel Immunocapture and Mass Spectrometry Techniques
Published on: January 12, 2024
Functional and structural characterization of a two-MAb cocktail for delayed treatment of enterovirus D68 infections
Chao Zhang1,2, Cong Xu3, Wenlong Dai2
1Joint Center for Infection and Immunity, Guangzhou Institute of Pediatrics, Department of Gastroenterology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
Abstract:
Enterovirus D68 (EV-D68) is an emerging pathogen associated with respiratory diseases and/or acute flaccid myelitis. Here, two MAbs, 2H12 and 8F12, raised against EV-D68 virus-like particle (VLP), show distinct preference in binding VLP and virion and in neutralizing different EV-D68 strains. A combination of 2H12 and 8F12 exhibits balanced and potent neutralization effects and confers broader protection in mice than single MAbs when given at onset of symptoms. Cryo-EM structures of EV-D68 virion complexed with 2H12 or 8F12 show that both antibodies bind to the canyon region of the virion, creating steric hindrance for sialic acid receptor binding. Additionally, 2H12 binding can impair virion integrity and trigger premature viral uncoating. We also capture an uncoating intermediate induced by 2H12 binding, not previously described for picornaviruses. Our study elucidates the structural basis and neutralizing mechanisms of the 2H12 and 8F12 MAbs and supports further development of the 2H12/8F12 cocktail as a broad-spectrum therapeutic agent against EV-D68 infections in humans.
Insights
Two novel monoclonal antibodies (MAbs), 2H12 and 8F12, offer potent neutralization against Enterovirus D68 (EV-D68) and related viruses. Their combined use provides broad protection, paving the way for a new therapeutic agent against EV-D68 infections.
Area of Science:
- Virology
- Immunology
- Structural Biology
Background:
- Enterovirus D68 (EV-D68) is an emerging pathogen causing respiratory illness and acute flaccid myelitis.
- Existing therapeutics for EV-D68 are limited, necessitating the development of novel antiviral strategies.
Purpose of the Study:
- To characterize two novel monoclonal antibodies (MAbs), 2H12 and 8F12, for their efficacy against EV-D68.
- To elucidate the structural basis and neutralizing mechanisms of these MAbs.
Main Methods:
- Generation of MAbs against EV-D68 virus-like particles (VLPs).
- Binding assays to VLP and virions.
- Neutralization assays across different EV-D68 strains.
- Cryo-electron microscopy (Cryo-EM) for structural determination.
- In vivo protection studies in mice.
Main Results:
- MAbs 2H12 and 8F12 display distinct binding preferences and neutralization capabilities.
- A combination of 2H12 and 8F12 demonstrated potent, balanced neutralization and broader protection in mice.
- Cryo-EM revealed antibodies binding the virion canyon, hindering receptor attachment.
- MAb 2H12 binding induced premature viral uncoating, revealing a novel intermediate.
Conclusions:
- The 2H12 and 8F12 MAbs target distinct mechanisms for EV-D68 neutralization.
- The combined MAb cocktail offers broad-spectrum protection against EV-D68.
- This MAb combination represents a promising therapeutic candidate for human EV-D68 infections.
