Progress in enterovirus D68-neutralizing antibodies and vaccines

Q: What is the clinical evidence from this study?

Study design: Review. Population: Enterovirus D68 (EV-D68) infection and acute flaccid myelitis. Intervention: EV-D68-neutralizing antibodies and vaccines.

Q: What does this research mean for the field?

While neutralizing antibodies and various vaccine platforms offer promising therapeutic and preventive strategies against EV-D68, successful countermeasure development must overcome key challenges including antigenic drift and blood-brain barrier penetration. Novelty: ClaimNovelty.SYNTHESIS. Consensus alignment: ConsensusAlignment.NEUTRAL.

Liting Wang; Jun Shen

doi:10.1128/jvi.00123-26

June 3, 2026Journal of VirologyOpen Access

Progress in enterovirus D68-neutralizing antibodies and vaccines

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Key result

Neutralizing antibodies and novel vaccines show preclinical promise for preventing and treating EV-D68 infection.

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Why the study?

Enterovirus D68 causes severe respiratory diseases and acute flaccid myelitis, but no licensed vaccines or therapeutics are currently available.

Key Points

To review the antigenic architecture of enterovirus D68 (EV-D68), mechanisms of neutralizing antibodies, and progress in therapeutic antibody and vaccine development.
Synthesized structural and immunological evidence detailing EV-D68 capsid topology, structural proteins (VP1–VP4), and symmetry axes.
Analyzed mechanisms of neutralizing monoclonal antibodies derived from human, mouse, and rhesus origins, focusing on receptor blockade and uncoating inhibition.
Evaluated preclinical vaccine platforms (inactivated, virus-like particles, nucleic acid) and evolutionary patterns across viral clades A through D.
Structural mapping reveals that antibodies targeting the conserved receptor-binding canyon surrounding the 5-fold axis provide broad cross-clade neutralization, whereas those targeting the 3-fold plateau exhibit narrow, strain-specific activity.
Evolutionary rate analysis of the immunodominant VP1 capsid gene showed continuous diversification at 0.0039 ± 0.0001 substitutions per site per year, driving antigenic drift and clade transitions.
Multiple preclinical monoclonal antibodies, including EV68-228-N and 15C5, confer in vivo protection, though antigenic variation and blood-brain barrier penetration remain major development challenges.

Structured PICO

P

Population

Animal models (including mice, rhesus macaques, cotton rats) and human-derived sources used for studying Enterovirus D68 (EV-D68) infection and immunity

I

Intervention

Enterovirus D68-neutralizing antibodies (mAbs and IVIG) and vaccine platforms (inactivated, VLP, and nucleic acid)

Limitations

Ongoing viral evolution and antigenic drift threaten the durability of neutralizing antibodies and vaccines.
The blood-brain barrier restricts antibody access to the central nervous system.
Immunological correlates of protection against acute flaccid myelitis remain poorly defined.
No EV-D68 vaccine candidates have yet entered human clinical trials.
Antigenic drift
Blood-brain barrier (BBB) penetration challenges
Viral escape risk and selection of variant viruses under antibody pressure
Donor-dependence and batch variability for polyclonal antibodies/IVIG

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Implication

This review outlines the structural targets, mechanisms of action, and preclinical development of neutralizing antibodies and vaccines against Enterovirus D68, highlighting their therapeutic and preventive potential for associated acute flaccid myelitis.

Abstract

Enterovirus D68 (EV-D68) causes severe respiratory diseases and acute flaccid myelitis (AFM), for which no licensed vaccines or therapeutics are currently available. Neutralizing antibodies (nAbs) block infection via binding capsid epitopes. This review summarizes the EV-D68 antigenic structure, nAb mechanisms (receptor blockade and conformational disruption), therapeutic prospects of nAbs, and vaccine progress (inactivated, virus-like particle [VLP], and nucleic acid). Key challenges, like antigenic drift and blood-brain barrier (BBB) penetration, are also highlighted to guide countermeasure development.

Discussion

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Cite This Study

Wang et al. (2026) conducted a review in Enterovirus D68 (EV-D68) infection and acute flaccid myelitis. EV-D68-neutralizing antibodies and vaccines was evaluated. Neutralizing antibodies and novel vaccine platforms (inactivated, virus-like particle, and nucleic acid) show preclinical promise for preventing and treating EV-D68 infection and associated acute flaccid myelitis.

synapsesocial.com/papers/6a2269c9763171746d548545 https://doi.org/10.1128/jvi.00123-26

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Progress in enterovirus D68-neutralizing antibodies and vaccines

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Key Points

Structured PICO

Limitations

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Implication

Abstract

Discussion

Cite This Study

Progress in enterovirus D68-neutralizing antibodies and vaccines

Figures

Key Points

Structured PICO

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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