Use of Synonymous Deoptimization to Derive Modified Live Attenuated Strains of Foot and Mouth Disease Virus
Foot-and-mouth disease (FMD) is one of the most economically important viral diseases that can affect livestock. In the last 70 years, use of an inactivated whole antigen vaccine has contributed to the eradication of disease from many developed nations. However, recent outbreaks in Europe and Easter...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-01-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2020.610286/full |
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| author | Fayna Diaz-San Segundo Gisselle N. Medina Gisselle N. Medina Edward Spinard Edward Spinard Anna Kloc Anna Kloc Elizabeth Ramirez-Medina Elizabeth Ramirez-Medina Paul Azzinaro Steffen Mueller Elizabeth Rieder Teresa de los Santos |
| author_facet | Fayna Diaz-San Segundo Gisselle N. Medina Gisselle N. Medina Edward Spinard Edward Spinard Anna Kloc Anna Kloc Elizabeth Ramirez-Medina Elizabeth Ramirez-Medina Paul Azzinaro Steffen Mueller Elizabeth Rieder Teresa de los Santos |
| author_sort | Fayna Diaz-San Segundo |
| collection | DOAJ |
| description | Foot-and-mouth disease (FMD) is one of the most economically important viral diseases that can affect livestock. In the last 70 years, use of an inactivated whole antigen vaccine has contributed to the eradication of disease from many developed nations. However, recent outbreaks in Europe and Eastern Asia demonstrated that infection can spread as wildfire causing economic and social devastation. Therefore, it is essential to develop new control strategies that could confer early protection and rapidly stop disease spread. Live attenuated vaccines (LAV) are one of the best choices to obtain a strong early and long-lasting protection against viral diseases. In proof of concept studies, we previously demonstrated that “synonymous codon deoptimization” could be applied to the P1 capsid coding region of the viral genome to derive attenuated FMDV serotype A12 strains. Here, we demonstrate that a similar approach can be extended to the highly conserved non-structural P2 and P3 coding regions, providing a backbone for multiple serotype FMDV LAV development. Engineered codon deoptimized P2, P3 or P2, and P3 combined regions were included into the A24Cruzeiro infectious clone optimized for vaccine production, resulting in viable progeny that exhibited different degrees of attenuation in cell culture, in mice, and in the natural host (swine). Derived strains were thoroughly characterized in vitro and in vivo. Our work demonstrates that overall, the entire FMDV genome tolerates codon deoptimization, highlighting the potential of using this technology to derive novel improved LAV candidates. |
| first_indexed | 2024-12-17T03:35:45Z |
| format | Article |
| id | doaj.art-52262a67286d49e79655c95c3eefa336 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-17T03:35:45Z |
| publishDate | 2021-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-52262a67286d49e79655c95c3eefa3362022-12-21T22:05:08ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2021-01-011110.3389/fmicb.2020.610286610286Use of Synonymous Deoptimization to Derive Modified Live Attenuated Strains of Foot and Mouth Disease VirusFayna Diaz-San Segundo0Gisselle N. Medina1Gisselle N. Medina2Edward Spinard3Edward Spinard4Anna Kloc5Anna Kloc6Elizabeth Ramirez-Medina7Elizabeth Ramirez-Medina8Paul Azzinaro9Steffen Mueller10Elizabeth Rieder11Teresa de los Santos12Plum Island Animal Disease Center (PIADC), Agricultural Research Service, United States Department of Agriculture, Greenport, NY, United StatesPlum Island Animal Disease Center (PIADC), Agricultural Research Service, United States Department of Agriculture, Greenport, NY, United StatesKansas State University College of Veterinary Medicine, Manhattan, KS, United StatesPlum Island Animal Disease Center (PIADC), Agricultural Research Service, United States Department of Agriculture, Greenport, NY, United StatesPIADC Research Participation Program, Oak Ridge Institute for Science and Education, Oak Ridge, TN, United StatesPlum Island Animal Disease Center (PIADC), Agricultural Research Service, United States Department of Agriculture, Greenport, NY, United StatesPIADC Research Participation Program, Oak Ridge Institute for Science and Education, Oak Ridge, TN, United StatesPlum Island Animal Disease Center (PIADC), Agricultural Research Service, United States Department of Agriculture, Greenport, NY, United StatesDepartment of Pathobiology and Veterinary Science, University of Connecticut, Storrs, CT, United StatesPlum Island Animal Disease Center (PIADC), Agricultural Research Service, United States Department of Agriculture, Greenport, NY, United StatesCodagenix, Inc., Farmingdale, NY, United StatesPlum Island Animal Disease Center (PIADC), Agricultural Research Service, United States Department of Agriculture, Greenport, NY, United StatesPlum Island Animal Disease Center (PIADC), Agricultural Research Service, United States Department of Agriculture, Greenport, NY, United StatesFoot-and-mouth disease (FMD) is one of the most economically important viral diseases that can affect livestock. In the last 70 years, use of an inactivated whole antigen vaccine has contributed to the eradication of disease from many developed nations. However, recent outbreaks in Europe and Eastern Asia demonstrated that infection can spread as wildfire causing economic and social devastation. Therefore, it is essential to develop new control strategies that could confer early protection and rapidly stop disease spread. Live attenuated vaccines (LAV) are one of the best choices to obtain a strong early and long-lasting protection against viral diseases. In proof of concept studies, we previously demonstrated that “synonymous codon deoptimization” could be applied to the P1 capsid coding region of the viral genome to derive attenuated FMDV serotype A12 strains. Here, we demonstrate that a similar approach can be extended to the highly conserved non-structural P2 and P3 coding regions, providing a backbone for multiple serotype FMDV LAV development. Engineered codon deoptimized P2, P3 or P2, and P3 combined regions were included into the A24Cruzeiro infectious clone optimized for vaccine production, resulting in viable progeny that exhibited different degrees of attenuation in cell culture, in mice, and in the natural host (swine). Derived strains were thoroughly characterized in vitro and in vivo. Our work demonstrates that overall, the entire FMDV genome tolerates codon deoptimization, highlighting the potential of using this technology to derive novel improved LAV candidates.https://www.frontiersin.org/articles/10.3389/fmicb.2020.610286/fullFMDVsynonymous deoptimizationcodon biasvaccineattenuationFMD |
| spellingShingle | Fayna Diaz-San Segundo Gisselle N. Medina Gisselle N. Medina Edward Spinard Edward Spinard Anna Kloc Anna Kloc Elizabeth Ramirez-Medina Elizabeth Ramirez-Medina Paul Azzinaro Steffen Mueller Elizabeth Rieder Teresa de los Santos Use of Synonymous Deoptimization to Derive Modified Live Attenuated Strains of Foot and Mouth Disease Virus Frontiers in Microbiology FMDV synonymous deoptimization codon bias vaccine attenuation FMD |
| title | Use of Synonymous Deoptimization to Derive Modified Live Attenuated Strains of Foot and Mouth Disease Virus |
| title_full | Use of Synonymous Deoptimization to Derive Modified Live Attenuated Strains of Foot and Mouth Disease Virus |
| title_fullStr | Use of Synonymous Deoptimization to Derive Modified Live Attenuated Strains of Foot and Mouth Disease Virus |
| title_full_unstemmed | Use of Synonymous Deoptimization to Derive Modified Live Attenuated Strains of Foot and Mouth Disease Virus |
| title_short | Use of Synonymous Deoptimization to Derive Modified Live Attenuated Strains of Foot and Mouth Disease Virus |
| title_sort | use of synonymous deoptimization to derive modified live attenuated strains of foot and mouth disease virus |
| topic | FMDV synonymous deoptimization codon bias vaccine attenuation FMD |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2020.610286/full |
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