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Open Access 01-12-2022 | Coxsackievirus | Research

Identification of a neutralizing linear epitope within the VP1 protein of coxsackievirus A10

Authors: Hanyu Zhu, Xin Liu, Yue Wu, Yunyi He, Huanying Zheng, Hongbo Liu, Qiliang Liu

Published in: Virology Journal | Issue 1/2022

Abstract

Background

Coxsackievirus A10 (CV-A10) is a leading cause of hand, foot, and mouth disease (HFMD). It is necessary to identify neutralizing epitopes to investigate and develop an epitope-based vaccine against CV-A10. The viral protein VP1 is the immunodominant capsid protein and contains the critical neutralizing epitope. However, neutralizing epitopes within VP1 protein of CV-A10 have not been well characterized.

Methods

Bioinformatics techniques were applied to predict linear epitopes on the CV-A10 VP1 protein. The advanced structural features of epitopes were analyzed by three-dimensional (3D) modeling. The anticipated epitope peptides were synthesized and used to immunize mice as antigens. ELISA and micro-neutralization assay were used to determine the specific IgG antibody and neutralizing antibody titers. The protective efficacy of the epitope peptides in vivo was evaluated using a passive immunization/challenge assay.

Results

Three linear epitopes (EP3, EP4, and EP5) were predicted on CV-A10 VP1, all spatially exposed on the capsid surface, and exhibited adequate immunogenicity. However, only EP4, corresponding to residues 162–176 of VP1, demonstrated potent neutralization against CV-A10. To determine the neutralizing capacity of EP4 further, EP4 double-peptide was synthesized and injected into mice. The mean neutralizing antibody titer of the anti-EP4 double-peptide sera was 1:50.79, which provided 40% protection against lethal infection with CV-A10 in neonatal mice. In addition, sequence and advanced structural analysis revealed that EP4 was highly conserved among representative strains of CV-A10 and localized in the EF loop region of VP1, like EV-A71 SP55 or CV-A16 PEP55.

Conclusions

These data demonstrate that EP4 is a specific linear neutralizing epitope on CV-A10 VP1. Its protective efficacy can be enhanced by increasing its copy number, which will be the foundation for developing a CV-A10 epitope-based vaccine.

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Title: Identification of a neutralizing linear epitope within the VP1 protein of coxsackievirus A10
Authors: Hanyu Zhu
Xin Liu
Yue Wu
Yunyi He
Huanying Zheng
Hongbo Liu
Qiliang Liu
Publication date: 01-12-2022
Publisher: BioMed Central
Keyword: Coxsackievirus
Published in: Virology Journal / Issue 1/2022
Electronic ISSN: 1743-422X
DOI: https://doi.org/10.1186/s12985-022-01939-3

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Identification of a neutralizing linear epitope within the VP1 protein of coxsackievirus A10

Abstract

Background

Methods

Results

Conclusions

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Abstract

Background

Methods

Results

Conclusions

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