Deletion Mutants of the Attenuated Recombinant ASF Virus, BA71ΔCD2, Show Decreased Vaccine Efficacy
African swine fever (ASF) has become the major threat to the global swine industry. Lack of available commercial vaccines complicates the implementation of global control strategies. So far, only live attenuated ASF viruses (ASFV) have demonstrated solid protection efficacy at the experimental level...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-08-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/13/9/1678 |
| _version_ | 1797517018069467136 |
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| author | Elisabeth Lopez Laia Bosch-Camós Elizabeth Ramirez-Medina Elizabeth Vuono Maria Jesus Navas Marta Muñoz Francesc Accensi Jinya Zhang Uxia Alonso Jordi Argilaguet Maria Luisa Salas Nikolay Anachkov Douglas P. Gladue Manuel V. Borca Sonia Pina-Pedrero Fernando Rodriguez |
| author_facet | Elisabeth Lopez Laia Bosch-Camós Elizabeth Ramirez-Medina Elizabeth Vuono Maria Jesus Navas Marta Muñoz Francesc Accensi Jinya Zhang Uxia Alonso Jordi Argilaguet Maria Luisa Salas Nikolay Anachkov Douglas P. Gladue Manuel V. Borca Sonia Pina-Pedrero Fernando Rodriguez |
| author_sort | Elisabeth Lopez |
| collection | DOAJ |
| description | African swine fever (ASF) has become the major threat to the global swine industry. Lack of available commercial vaccines complicates the implementation of global control strategies. So far, only live attenuated ASF viruses (ASFV) have demonstrated solid protection efficacy at the experimental level. The implementation of molecular techniques has allowed the generation of a collection of deletion mutants lacking ASFV-specific virulence factors, some of them with promising potential as vaccine candidates against the pandemic genotype II ASFV strain currently circulating in Africa, Europe, Asia and Oceania. Despite promising results, there is room for improvement, mainly from the biosafety point of view. Aiming to improve the safety of BA71∆CD2, a cross-protective recombinant live attenuated virus (LAV) lacking the ASFV CD2v gene (encoding β-glucuronidase as a reporter gene) available in our laboratory, three new recombinants were generated using BA71∆CD2 as a template: the single mutant BA71∆CD2<i>f</i>, this time containing the fluorescent mCherry reporter gene instead of CD2v, and two double recombinants lacking CD2v and either the lectin gene (EP153R) or the uridine kinase (UK) gene (DP96R). Comparative in vivo experiments using BA71∆CD2<i>f</i>, BA71∆CD2DP96R and BA71∆CD2EP153R recombinant viruses as immunogens, demonstrated that deletion of either DP96R or EP153R from BA71∆CD2<i>f</i> decreases vaccine efficacy and does not improve safety. Our results additionally confirm ASFV challenge as the only available method today to evaluate the protective efficacy of any experimental vaccine. We believe that understanding the fine equilibrium between attenuation and inducing protection in vivo deserves further study and might contribute to more rational vaccine designs in the future. |
| first_indexed | 2024-03-10T07:09:05Z |
| format | Article |
| id | doaj.art-d721e4b11d944268a86207e30a42266b |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T07:09:05Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-d721e4b11d944268a86207e30a42266b2023-11-22T15:36:21ZengMDPI AGViruses1999-49152021-08-01139167810.3390/v13091678Deletion Mutants of the Attenuated Recombinant ASF Virus, BA71ΔCD2, Show Decreased Vaccine EfficacyElisabeth Lopez0Laia Bosch-Camós1Elizabeth Ramirez-Medina2Elizabeth Vuono3Maria Jesus Navas4Marta Muñoz5Francesc Accensi6Jinya Zhang7Uxia Alonso8Jordi Argilaguet9Maria Luisa Salas10Nikolay Anachkov11Douglas P. Gladue12Manuel V. Borca13Sonia Pina-Pedrero14Fernando Rodriguez15IRTA, Centre de Recerca en Sanitat Animal (IRTA-CReSA), Campus de la Universitat Autonoma de Barcelona, 08193 Bellaterra, SpainIRTA, Centre de Recerca en Sanitat Animal (IRTA-CReSA), Campus de la Universitat Autonoma de Barcelona, 08193 Bellaterra, SpainUSDA Plum Island Animal Disease Center, Agricultural Research Service, United States Department of Agriculture, Greenport, NY 11944, USAUSDA Plum Island Animal Disease Center, Agricultural Research Service, United States Department of Agriculture, Greenport, NY 11944, USAIRTA, Centre de Recerca en Sanitat Animal (IRTA-CReSA), Campus de la Universitat Autonoma de Barcelona, 08193 Bellaterra, SpainIRTA, Centre de Recerca en Sanitat Animal (IRTA-CReSA), Campus de la Universitat Autonoma de Barcelona, 08193 Bellaterra, SpainIRTA, Centre de Recerca en Sanitat Animal (IRTA-CReSA), Campus de la Universitat Autonoma de Barcelona, 08193 Bellaterra, SpainIRTA, Centre de Recerca en Sanitat Animal (IRTA-CReSA), Campus de la Universitat Autonoma de Barcelona, 08193 Bellaterra, SpainIRTA, Centre de Recerca en Sanitat Animal (IRTA-CReSA), Campus de la Universitat Autonoma de Barcelona, 08193 Bellaterra, SpainIRTA, Centre de Recerca en Sanitat Animal (IRTA-CReSA), Campus de la Universitat Autonoma de Barcelona, 08193 Bellaterra, SpainCentro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Campus de la Universidad Autònoma de Madrid, 28049 Madrid, SpainBiologics Development, Huvepharma, 3A Nikolay Haytov Street, 1113 Sofia, BulgariaUSDA Plum Island Animal Disease Center, Agricultural Research Service, United States Department of Agriculture, Greenport, NY 11944, USAUSDA Plum Island Animal Disease Center, Agricultural Research Service, United States Department of Agriculture, Greenport, NY 11944, USAIRTA, Centre de Recerca en Sanitat Animal (IRTA-CReSA), Campus de la Universitat Autonoma de Barcelona, 08193 Bellaterra, SpainIRTA, Centre de Recerca en Sanitat Animal (IRTA-CReSA), Campus de la Universitat Autonoma de Barcelona, 08193 Bellaterra, SpainAfrican swine fever (ASF) has become the major threat to the global swine industry. Lack of available commercial vaccines complicates the implementation of global control strategies. So far, only live attenuated ASF viruses (ASFV) have demonstrated solid protection efficacy at the experimental level. The implementation of molecular techniques has allowed the generation of a collection of deletion mutants lacking ASFV-specific virulence factors, some of them with promising potential as vaccine candidates against the pandemic genotype II ASFV strain currently circulating in Africa, Europe, Asia and Oceania. Despite promising results, there is room for improvement, mainly from the biosafety point of view. Aiming to improve the safety of BA71∆CD2, a cross-protective recombinant live attenuated virus (LAV) lacking the ASFV CD2v gene (encoding β-glucuronidase as a reporter gene) available in our laboratory, three new recombinants were generated using BA71∆CD2 as a template: the single mutant BA71∆CD2<i>f</i>, this time containing the fluorescent mCherry reporter gene instead of CD2v, and two double recombinants lacking CD2v and either the lectin gene (EP153R) or the uridine kinase (UK) gene (DP96R). Comparative in vivo experiments using BA71∆CD2<i>f</i>, BA71∆CD2DP96R and BA71∆CD2EP153R recombinant viruses as immunogens, demonstrated that deletion of either DP96R or EP153R from BA71∆CD2<i>f</i> decreases vaccine efficacy and does not improve safety. Our results additionally confirm ASFV challenge as the only available method today to evaluate the protective efficacy of any experimental vaccine. We believe that understanding the fine equilibrium between attenuation and inducing protection in vivo deserves further study and might contribute to more rational vaccine designs in the future.https://www.mdpi.com/1999-4915/13/9/1678African swine fever (ASF)African swine fever virus (ASFV)live attenuated virus (LAV)vaccinevirulence factordouble mutant |
| spellingShingle | Elisabeth Lopez Laia Bosch-Camós Elizabeth Ramirez-Medina Elizabeth Vuono Maria Jesus Navas Marta Muñoz Francesc Accensi Jinya Zhang Uxia Alonso Jordi Argilaguet Maria Luisa Salas Nikolay Anachkov Douglas P. Gladue Manuel V. Borca Sonia Pina-Pedrero Fernando Rodriguez Deletion Mutants of the Attenuated Recombinant ASF Virus, BA71ΔCD2, Show Decreased Vaccine Efficacy Viruses African swine fever (ASF) African swine fever virus (ASFV) live attenuated virus (LAV) vaccine virulence factor double mutant |
| title | Deletion Mutants of the Attenuated Recombinant ASF Virus, BA71ΔCD2, Show Decreased Vaccine Efficacy |
| title_full | Deletion Mutants of the Attenuated Recombinant ASF Virus, BA71ΔCD2, Show Decreased Vaccine Efficacy |
| title_fullStr | Deletion Mutants of the Attenuated Recombinant ASF Virus, BA71ΔCD2, Show Decreased Vaccine Efficacy |
| title_full_unstemmed | Deletion Mutants of the Attenuated Recombinant ASF Virus, BA71ΔCD2, Show Decreased Vaccine Efficacy |
| title_short | Deletion Mutants of the Attenuated Recombinant ASF Virus, BA71ΔCD2, Show Decreased Vaccine Efficacy |
| title_sort | deletion mutants of the attenuated recombinant asf virus ba71δcd2 show decreased vaccine efficacy |
| topic | African swine fever (ASF) African swine fever virus (ASFV) live attenuated virus (LAV) vaccine virulence factor double mutant |
| url | https://www.mdpi.com/1999-4915/13/9/1678 |
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