Enterovirus A71 containing codon-deoptimized VP1 and high-fidelity polymerase as next-generation vaccine candidate

Yi Hsuan Tsai, Sheng Wen Huang, Wen Sheng Hsieh, Cheng Kai Cheng, Chuan-Fa Chang, Ya Fang Wang, Jen-Ren Wang

研究成果: Article

1 引文 (Scopus)

摘要

Enterovirus A71 (EV-A71) is a major pathogen that causes hand-foot- and-mouth disease (HFMD), which occasionally results in severe neurological complications. In this study, we developed four EV-A71 (rgEV-A71) strains by reverse genetics procedures as possible vaccine candidates. The four rgEV-A71 viruses contained various codon-deoptimized VP1 capsid proteins (VP1-CD) and showed replication rates and antigenicity similar to that of the wild-type virus, while a fifth virus, rg4643C4VP-CD, was unable to form plaques but was still able to be examined by median tissue culture infectious dose (TCID50) titers, which were similar to those of the others, indicating the effect of CD on plaque formation. However, the genome stability showed that there were some mutations which appeared during just one passage of the VP1-CD viruses. Thus, we further constructed VP1-CD rgEV-A71 containing high-fidelity determinants in 3D polymerase (CD-HF), and the number of mutations in CD-HF rgEV-A71 was shown to have decreased. The CD-HF viruses showed less virulence than the parental strain in a mouse infection model. After 14 days postimmunization, antibody titers had increased in mice infected with CD-HF viruses. The mouse antisera showed similar neutralizing antibody titers against various CD-HF viruses and different genotypes of EV-A71. The study demonstrates the proof of concept that VP1 codon deoptimization combined with high-fidelity 3D polymerase decreased EV-A71 mutations and virulence in mice but retained their antigenicity, indicating it is a good candidate for next-generation EV-A71 vaccine development.

原文English
文章編號e02308-18
期刊Journal of Virology
93
發行號13
DOIs
出版狀態Published - 2019 一月 1

指紋

Enterovirus
codons
Codon
Vaccines
vaccines
Viruses
viruses
Capsid Proteins
coat proteins
mice
mutation
Mutation
Virulence
virulence
hand, foot and mouth disease
Hand, Foot and Mouth Disease
Reverse Genetics
Genomic Instability
vaccine development
Neutralizing Antibodies

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

引用此文

Tsai, Yi Hsuan ; Huang, Sheng Wen ; Hsieh, Wen Sheng ; Cheng, Cheng Kai ; Chang, Chuan-Fa ; Wang, Ya Fang ; Wang, Jen-Ren. / Enterovirus A71 containing codon-deoptimized VP1 and high-fidelity polymerase as next-generation vaccine candidate. 於: Journal of Virology. 2019 ; 卷 93, 編號 13.
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abstract = "Enterovirus A71 (EV-A71) is a major pathogen that causes hand-foot- and-mouth disease (HFMD), which occasionally results in severe neurological complications. In this study, we developed four EV-A71 (rgEV-A71) strains by reverse genetics procedures as possible vaccine candidates. The four rgEV-A71 viruses contained various codon-deoptimized VP1 capsid proteins (VP1-CD) and showed replication rates and antigenicity similar to that of the wild-type virus, while a fifth virus, rg4643C4VP-CD, was unable to form plaques but was still able to be examined by median tissue culture infectious dose (TCID50) titers, which were similar to those of the others, indicating the effect of CD on plaque formation. However, the genome stability showed that there were some mutations which appeared during just one passage of the VP1-CD viruses. Thus, we further constructed VP1-CD rgEV-A71 containing high-fidelity determinants in 3D polymerase (CD-HF), and the number of mutations in CD-HF rgEV-A71 was shown to have decreased. The CD-HF viruses showed less virulence than the parental strain in a mouse infection model. After 14 days postimmunization, antibody titers had increased in mice infected with CD-HF viruses. The mouse antisera showed similar neutralizing antibody titers against various CD-HF viruses and different genotypes of EV-A71. The study demonstrates the proof of concept that VP1 codon deoptimization combined with high-fidelity 3D polymerase decreased EV-A71 mutations and virulence in mice but retained their antigenicity, indicating it is a good candidate for next-generation EV-A71 vaccine development.",
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Enterovirus A71 containing codon-deoptimized VP1 and high-fidelity polymerase as next-generation vaccine candidate. / Tsai, Yi Hsuan; Huang, Sheng Wen; Hsieh, Wen Sheng; Cheng, Cheng Kai; Chang, Chuan-Fa; Wang, Ya Fang; Wang, Jen-Ren.

於: Journal of Virology, 卷 93, 編號 13, e02308-18, 01.01.2019.

研究成果: Article

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AU - Hsieh, Wen Sheng

AU - Cheng, Cheng Kai

AU - Chang, Chuan-Fa

AU - Wang, Ya Fang

AU - Wang, Jen-Ren

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AB - Enterovirus A71 (EV-A71) is a major pathogen that causes hand-foot- and-mouth disease (HFMD), which occasionally results in severe neurological complications. In this study, we developed four EV-A71 (rgEV-A71) strains by reverse genetics procedures as possible vaccine candidates. The four rgEV-A71 viruses contained various codon-deoptimized VP1 capsid proteins (VP1-CD) and showed replication rates and antigenicity similar to that of the wild-type virus, while a fifth virus, rg4643C4VP-CD, was unable to form plaques but was still able to be examined by median tissue culture infectious dose (TCID50) titers, which were similar to those of the others, indicating the effect of CD on plaque formation. However, the genome stability showed that there were some mutations which appeared during just one passage of the VP1-CD viruses. Thus, we further constructed VP1-CD rgEV-A71 containing high-fidelity determinants in 3D polymerase (CD-HF), and the number of mutations in CD-HF rgEV-A71 was shown to have decreased. The CD-HF viruses showed less virulence than the parental strain in a mouse infection model. After 14 days postimmunization, antibody titers had increased in mice infected with CD-HF viruses. The mouse antisera showed similar neutralizing antibody titers against various CD-HF viruses and different genotypes of EV-A71. The study demonstrates the proof of concept that VP1 codon deoptimization combined with high-fidelity 3D polymerase decreased EV-A71 mutations and virulence in mice but retained their antigenicity, indicating it is a good candidate for next-generation EV-A71 vaccine development.

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