Development of live attenuated Enterovirus 71 vaccine strains that confer protection against lethal challenge in mice
Besides causing mild hand, foot and mouth infections, Enterovirus A71 (EV-A71) is associated with neurological complications and fatality. With concerns about rising EV-A71 virulence, there is an urgency for more effective vaccines. The live attenuated vaccine (LAV) is a more valuable vaccine as it...
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Nature Research
2019
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| author | Yee, Pinn Tsin Isabel Tan, Soon Hao Ong, Kien Chai Tan, Kuan Onn Wong, Kum Thong Hassan, Sharifah Syed Poh, Chit Laa |
| author_facet | Yee, Pinn Tsin Isabel Tan, Soon Hao Ong, Kien Chai Tan, Kuan Onn Wong, Kum Thong Hassan, Sharifah Syed Poh, Chit Laa |
| author_sort | Yee, Pinn Tsin Isabel |
| collection | UM |
| description | Besides causing mild hand, foot and mouth infections, Enterovirus A71 (EV-A71) is associated with neurological complications and fatality. With concerns about rising EV-A71 virulence, there is an urgency for more effective vaccines. The live attenuated vaccine (LAV) is a more valuable vaccine as it can elicit both humoral and cellular immune responses. A miRNA-based vaccine strain (pIY) carrying let-7a and miR-124a target genes in the EV-A71 genome which has a partial deletion in the 5′NTR (∆11 bp) and G64R mutation (3D p ° l ) was designed. The viral RNA copy number and viral titers of the pIY strain were significantly lower in SHSY-5Y cells that expressed both let-7a and miR-124a. Inhibition of the cognate miRNAs expressed in RD and SHSY-5Y cells demonstrated de-repression of viral mRNA translation. A previously constructed multiply mutated strain, MMS and the pIY vaccine strain were assessed in their ability to protect 4-week old mice from hind limb paralysis. The MMS showed higher amounts of IFN-γ ex vivo than the pIY vaccine strain. There was absence of EV-A71 antigen in the skeletal muscles and spinal cord micrographs of mice vaccinated with the MMS and pIY strains. The MMS and pIY strains are promising LAV candidates developed against severe EV-A71 infections. © 2019, The Author(s). |
| first_indexed | 2024-03-06T05:58:53Z |
| format | Article |
| id | um.eprints-23102 |
| institution | Universiti Malaya |
| last_indexed | 2024-03-06T05:58:53Z |
| publishDate | 2019 |
| publisher | Nature Research |
| record_format | dspace |
| spelling | um.eprints-231022019-11-27T02:00:29Z http://eprints.um.edu.my/23102/ Development of live attenuated Enterovirus 71 vaccine strains that confer protection against lethal challenge in mice Yee, Pinn Tsin Isabel Tan, Soon Hao Ong, Kien Chai Tan, Kuan Onn Wong, Kum Thong Hassan, Sharifah Syed Poh, Chit Laa R Medicine Besides causing mild hand, foot and mouth infections, Enterovirus A71 (EV-A71) is associated with neurological complications and fatality. With concerns about rising EV-A71 virulence, there is an urgency for more effective vaccines. The live attenuated vaccine (LAV) is a more valuable vaccine as it can elicit both humoral and cellular immune responses. A miRNA-based vaccine strain (pIY) carrying let-7a and miR-124a target genes in the EV-A71 genome which has a partial deletion in the 5′NTR (∆11 bp) and G64R mutation (3D p ° l ) was designed. The viral RNA copy number and viral titers of the pIY strain were significantly lower in SHSY-5Y cells that expressed both let-7a and miR-124a. Inhibition of the cognate miRNAs expressed in RD and SHSY-5Y cells demonstrated de-repression of viral mRNA translation. A previously constructed multiply mutated strain, MMS and the pIY vaccine strain were assessed in their ability to protect 4-week old mice from hind limb paralysis. The MMS showed higher amounts of IFN-γ ex vivo than the pIY vaccine strain. There was absence of EV-A71 antigen in the skeletal muscles and spinal cord micrographs of mice vaccinated with the MMS and pIY strains. The MMS and pIY strains are promising LAV candidates developed against severe EV-A71 infections. © 2019, The Author(s). Nature Research 2019 Article PeerReviewed Yee, Pinn Tsin Isabel and Tan, Soon Hao and Ong, Kien Chai and Tan, Kuan Onn and Wong, Kum Thong and Hassan, Sharifah Syed and Poh, Chit Laa (2019) Development of live attenuated Enterovirus 71 vaccine strains that confer protection against lethal challenge in mice. Scientific Reports, 9 (1). p. 4805. ISSN 2045-2322, DOI https://doi.org/10.1038/s41598-019-41285-z <https://doi.org/10.1038/s41598-019-41285-z>. https://doi.org/10.1038/s41598-019-41285-z doi:10.1038/s41598-019-41285-z |
| spellingShingle | R Medicine Yee, Pinn Tsin Isabel Tan, Soon Hao Ong, Kien Chai Tan, Kuan Onn Wong, Kum Thong Hassan, Sharifah Syed Poh, Chit Laa Development of live attenuated Enterovirus 71 vaccine strains that confer protection against lethal challenge in mice |
| title | Development of live attenuated Enterovirus 71 vaccine strains that confer protection against lethal challenge in mice |
| title_full | Development of live attenuated Enterovirus 71 vaccine strains that confer protection against lethal challenge in mice |
| title_fullStr | Development of live attenuated Enterovirus 71 vaccine strains that confer protection against lethal challenge in mice |
| title_full_unstemmed | Development of live attenuated Enterovirus 71 vaccine strains that confer protection against lethal challenge in mice |
| title_short | Development of live attenuated Enterovirus 71 vaccine strains that confer protection against lethal challenge in mice |
| title_sort | development of live attenuated enterovirus 71 vaccine strains that confer protection against lethal challenge in mice |
| topic | R Medicine |
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