Identification of a neutralizing linear epitope within the VP1 protein of coxsackievirus A10
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 th...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-12-01
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| Series: | Virology Journal |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12985-022-01939-3 |
| _version_ | 1811315558745899008 |
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| author | Hanyu Zhu Xin Liu Yue Wu Yunyi He Huanying Zheng Hongbo Liu Qiliang Liu |
| author_facet | Hanyu Zhu Xin Liu Yue Wu Yunyi He Huanying Zheng Hongbo Liu Qiliang Liu |
| author_sort | Hanyu Zhu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T11:33:30Z |
| format | Article |
| id | doaj.art-e4c3d175c524497581de9492d40e6d83 |
| institution | Directory Open Access Journal |
| issn | 1743-422X |
| language | English |
| last_indexed | 2024-04-13T11:33:30Z |
| publishDate | 2022-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Virology Journal |
| spelling | doaj.art-e4c3d175c524497581de9492d40e6d832022-12-22T02:48:31ZengBMCVirology Journal1743-422X2022-12-0119111010.1186/s12985-022-01939-3Identification of a neutralizing linear epitope within the VP1 protein of coxsackievirus A10Hanyu Zhu0Xin Liu1Yue Wu2Yunyi He3Huanying Zheng4Hongbo Liu5Qiliang Liu6College of Intelligent Medicine and Biotechnology, Guilin Medical UniversityCollege of Intelligent Medicine and Biotechnology, Guilin Medical UniversityDepartment of Laboratory Medicine, The Second Affiliated Hospital of Guilin Medical UniversityDepartment of Laboratory Medicine, The Second Affiliated Hospital of Guilin Medical UniversityGuangdong Provincial Institute of Public Health, Guangdong Provincial Center for Disease Control and PreventionDepartment of Laboratory Medicine, The Second Affiliated Hospital of Guilin Medical UniversityCollege of Intelligent Medicine and Biotechnology, Guilin Medical UniversityAbstract 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.https://doi.org/10.1186/s12985-022-01939-3Coxsackievirus A10EpitopeNeutralizationBioinformatics |
| spellingShingle | Hanyu Zhu Xin Liu Yue Wu Yunyi He Huanying Zheng Hongbo Liu Qiliang Liu Identification of a neutralizing linear epitope within the VP1 protein of coxsackievirus A10 Virology Journal Coxsackievirus A10 Epitope Neutralization Bioinformatics |
| title | Identification of a neutralizing linear epitope within the VP1 protein of coxsackievirus A10 |
| title_full | Identification of a neutralizing linear epitope within the VP1 protein of coxsackievirus A10 |
| title_fullStr | Identification of a neutralizing linear epitope within the VP1 protein of coxsackievirus A10 |
| title_full_unstemmed | Identification of a neutralizing linear epitope within the VP1 protein of coxsackievirus A10 |
| title_short | Identification of a neutralizing linear epitope within the VP1 protein of coxsackievirus A10 |
| title_sort | identification of a neutralizing linear epitope within the vp1 protein of coxsackievirus a10 |
| topic | Coxsackievirus A10 Epitope Neutralization Bioinformatics |
| url | https://doi.org/10.1186/s12985-022-01939-3 |
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