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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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Autores principales: Lopez, Elisabeth, Bosch-Camós, Laia, Ramirez-Medina, Elizabeth, Vuono, Elizabeth, Navas, Maria Jesus, Muñoz, Marta, Accensi, Francesc, Zhang, Jinya, Alonso, Uxia, Argilaguet, Jordi, Salas, Maria Luisa, Anachkov, Nikolay, Gladue, Douglas P., Borca, Manuel V., Pina-Pedrero, Sonia, Rodriguez, Fernando
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8473413/
https://www.ncbi.nlm.nih.gov/pubmed/34578263
http://dx.doi.org/10.3390/v13091678
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author Lopez, Elisabeth
Bosch-Camós, Laia
Ramirez-Medina, Elizabeth
Vuono, Elizabeth
Navas, Maria Jesus
Muñoz, Marta
Accensi, Francesc
Zhang, Jinya
Alonso, Uxia
Argilaguet, Jordi
Salas, Maria Luisa
Anachkov, Nikolay
Gladue, Douglas P.
Borca, Manuel V.
Pina-Pedrero, Sonia
Rodriguez, Fernando
author_facet Lopez, Elisabeth
Bosch-Camós, Laia
Ramirez-Medina, Elizabeth
Vuono, Elizabeth
Navas, Maria Jesus
Muñoz, Marta
Accensi, Francesc
Zhang, Jinya
Alonso, Uxia
Argilaguet, Jordi
Salas, Maria Luisa
Anachkov, Nikolay
Gladue, Douglas P.
Borca, Manuel V.
Pina-Pedrero, Sonia
Rodriguez, Fernando
author_sort Lopez, Elisabeth
collection PubMed
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∆CD2f, 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∆CD2f, BA71∆CD2DP96R and BA71∆CD2EP153R recombinant viruses as immunogens, demonstrated that deletion of either DP96R or EP153R from BA71∆CD2f 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.
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spelling pubmed-84734132021-09-28 Deletion Mutants of the Attenuated Recombinant ASF Virus, BA71ΔCD2, Show Decreased Vaccine Efficacy Lopez, Elisabeth Bosch-Camós, Laia Ramirez-Medina, Elizabeth Vuono, Elizabeth Navas, Maria Jesus Muñoz, Marta Accensi, Francesc Zhang, Jinya Alonso, Uxia Argilaguet, Jordi Salas, Maria Luisa Anachkov, Nikolay Gladue, Douglas P. Borca, Manuel V. Pina-Pedrero, Sonia Rodriguez, Fernando Viruses Article 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∆CD2f, 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∆CD2f, BA71∆CD2DP96R and BA71∆CD2EP153R recombinant viruses as immunogens, demonstrated that deletion of either DP96R or EP153R from BA71∆CD2f 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. MDPI 2021-08-25 /pmc/articles/PMC8473413/ /pubmed/34578263 http://dx.doi.org/10.3390/v13091678 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lopez, Elisabeth
Bosch-Camós, Laia
Ramirez-Medina, Elizabeth
Vuono, Elizabeth
Navas, Maria Jesus
Muñoz, Marta
Accensi, Francesc
Zhang, Jinya
Alonso, Uxia
Argilaguet, Jordi
Salas, Maria Luisa
Anachkov, Nikolay
Gladue, Douglas P.
Borca, Manuel V.
Pina-Pedrero, Sonia
Rodriguez, Fernando
Deletion Mutants of the Attenuated Recombinant ASF Virus, BA71ΔCD2, Show Decreased Vaccine Efficacy
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 Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8473413/
https://www.ncbi.nlm.nih.gov/pubmed/34578263
http://dx.doi.org/10.3390/v13091678
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