Substitution of Coxsackievirus A16 VP1 BC and EF Loop Altered the Protective Immune Responses in Chimera Enterovirus A71
Hand, foot and mouth disease (HFMD) is a childhood disease caused by enterovirus A71 (EV-A71) and coxsackievirus A16 (CV-A16). Capsid loops are important epitopes for EV-A71 and CV-A16. Seven chimeric EV-A71 (ChiE71) involving VP1 BC (45.5% similarity), DE, EF, GH and HI loops, VP2 EF loop and VP3 G...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-08-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/11/8/1363 |
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| author | Xiu Hui Tan Wei Lim Chong Vannajan Sanghiran Lee Syahril Abdullah Kartini Jasni Saiful Qushairi Suarni David Perera I-Ching Sam Yoke Fun Chan |
| author_facet | Xiu Hui Tan Wei Lim Chong Vannajan Sanghiran Lee Syahril Abdullah Kartini Jasni Saiful Qushairi Suarni David Perera I-Ching Sam Yoke Fun Chan |
| author_sort | Xiu Hui Tan |
| collection | DOAJ |
| description | Hand, foot and mouth disease (HFMD) is a childhood disease caused by enterovirus A71 (EV-A71) and coxsackievirus A16 (CV-A16). Capsid loops are important epitopes for EV-A71 and CV-A16. Seven chimeric EV-A71 (ChiE71) involving VP1 BC (45.5% similarity), DE, EF, GH and HI loops, VP2 EF loop and VP3 GH loop (91.3% similarity) were substituted with corresponding CV-A16 loops. Only ChiE71-1-BC, ChiE71-1-EF, ChiE71-1-GH and ChiE71-3-GH were viable. EV-A71 and CV-A16 antiserum neutralized ChiE71-1-BC and ChiE71-1-EF. Mice immunized with inactivated ChiE71 elicited high IgG, IFN-γ, IL-2, IL-4 and IL-10. Neonatal mice receiving passive transfer of WT EV-A71, ChiE71-1-EF and ChiE71-1-BC immune sera had 100%, 80.0% and no survival, respectively, against lethal challenges with EV-A71, suggesting that the substituted CV-A16 loops disrupted EV-A71 immunogenicity. Passive transfer of CV-A16, ChiE71-1-EF and ChiE71-1-BC immune sera provided 40.0%, 20.0% and 42.9% survival, respectively, against CV-A16. One-day-old neonatal mice immunized with WT EV-A71, ChiE71-1-BC, ChiE71-1-EF and CV-A16 achieved 62.5%, 60.0%, 57.1%, and no survival, respectively, after the EV-A71 challenge. Active immunization using CV-A16 provided full protection while WT EV-A71, ChiE71-1-BC and ChiE71-1-EF immunization showed partial cross-protection in CV-A16 lethal challenge with survival rates of 50.0%, 20.0% and 40%, respectively. Disruption of a capsid loop could affect virus immunogenicity, and future vaccine design should include conservation of the enterovirus capsid loops. |
| first_indexed | 2024-03-10T23:31:43Z |
| format | Article |
| id | doaj.art-8510d684c40e45e396dbba2fc4c754d1 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-10T23:31:43Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-8510d684c40e45e396dbba2fc4c754d12023-11-19T03:18:07ZengMDPI AGVaccines2076-393X2023-08-01118136310.3390/vaccines11081363Substitution of Coxsackievirus A16 VP1 BC and EF Loop Altered the Protective Immune Responses in Chimera Enterovirus A71Xiu Hui Tan0Wei Lim Chong1Vannajan Sanghiran Lee2Syahril Abdullah3Kartini Jasni4Saiful Qushairi Suarni5David Perera6I-Ching Sam7Yoke Fun Chan8Department of Medical Microbiology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur 50603, MalaysiaDepartment of Chemistry, Center of Theoretical and Computational Physics, Faculty of Science, Universiti Malaya, Kuala Lumpur 50603, MalaysiaDepartment of Chemistry, Center of Theoretical and Computational Physics, Faculty of Science, Universiti Malaya, Kuala Lumpur 50603, MalaysiaDepartment of Biomedical Sciences, Faculty of Medicine & Health Sciences, Universiti Putra Malaysia, Serdang 43400, MalaysiaComparative Medicine and Technology Unit, Institute of Bioscience, Universiti Putra Malaysia, Serdang 43400, MalaysiaComparative Medicine and Technology Unit, Institute of Bioscience, Universiti Putra Malaysia, Serdang 43400, MalaysiaInstitute of Health and Community Medicine, Universiti Malaysia Sarawak, Kota Samarahan 94300, MalaysiaDepartment of Medical Microbiology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur 50603, MalaysiaDepartment of Medical Microbiology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur 50603, MalaysiaHand, foot and mouth disease (HFMD) is a childhood disease caused by enterovirus A71 (EV-A71) and coxsackievirus A16 (CV-A16). Capsid loops are important epitopes for EV-A71 and CV-A16. Seven chimeric EV-A71 (ChiE71) involving VP1 BC (45.5% similarity), DE, EF, GH and HI loops, VP2 EF loop and VP3 GH loop (91.3% similarity) were substituted with corresponding CV-A16 loops. Only ChiE71-1-BC, ChiE71-1-EF, ChiE71-1-GH and ChiE71-3-GH were viable. EV-A71 and CV-A16 antiserum neutralized ChiE71-1-BC and ChiE71-1-EF. Mice immunized with inactivated ChiE71 elicited high IgG, IFN-γ, IL-2, IL-4 and IL-10. Neonatal mice receiving passive transfer of WT EV-A71, ChiE71-1-EF and ChiE71-1-BC immune sera had 100%, 80.0% and no survival, respectively, against lethal challenges with EV-A71, suggesting that the substituted CV-A16 loops disrupted EV-A71 immunogenicity. Passive transfer of CV-A16, ChiE71-1-EF and ChiE71-1-BC immune sera provided 40.0%, 20.0% and 42.9% survival, respectively, against CV-A16. One-day-old neonatal mice immunized with WT EV-A71, ChiE71-1-BC, ChiE71-1-EF and CV-A16 achieved 62.5%, 60.0%, 57.1%, and no survival, respectively, after the EV-A71 challenge. Active immunization using CV-A16 provided full protection while WT EV-A71, ChiE71-1-BC and ChiE71-1-EF immunization showed partial cross-protection in CV-A16 lethal challenge with survival rates of 50.0%, 20.0% and 40%, respectively. Disruption of a capsid loop could affect virus immunogenicity, and future vaccine design should include conservation of the enterovirus capsid loops.https://www.mdpi.com/2076-393X/11/8/1363enterovirus A71coxsackievirus A16enterovirushandfoot and mouth diseasecapsid loop |
| spellingShingle | Xiu Hui Tan Wei Lim Chong Vannajan Sanghiran Lee Syahril Abdullah Kartini Jasni Saiful Qushairi Suarni David Perera I-Ching Sam Yoke Fun Chan Substitution of Coxsackievirus A16 VP1 BC and EF Loop Altered the Protective Immune Responses in Chimera Enterovirus A71 Vaccines enterovirus A71 coxsackievirus A16 enterovirus hand foot and mouth disease capsid loop |
| title | Substitution of Coxsackievirus A16 VP1 BC and EF Loop Altered the Protective Immune Responses in Chimera Enterovirus A71 |
| title_full | Substitution of Coxsackievirus A16 VP1 BC and EF Loop Altered the Protective Immune Responses in Chimera Enterovirus A71 |
| title_fullStr | Substitution of Coxsackievirus A16 VP1 BC and EF Loop Altered the Protective Immune Responses in Chimera Enterovirus A71 |
| title_full_unstemmed | Substitution of Coxsackievirus A16 VP1 BC and EF Loop Altered the Protective Immune Responses in Chimera Enterovirus A71 |
| title_short | Substitution of Coxsackievirus A16 VP1 BC and EF Loop Altered the Protective Immune Responses in Chimera Enterovirus A71 |
| title_sort | substitution of coxsackievirus a16 vp1 bc and ef loop altered the protective immune responses in chimera enterovirus a71 |
| topic | enterovirus A71 coxsackievirus A16 enterovirus hand foot and mouth disease capsid loop |
| url | https://www.mdpi.com/2076-393X/11/8/1363 |
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