Deletion Mutants of the Attenuated Recombinant ASF Virus, BA71ΔCD2, Show Decreased Vaccine Efficacy
López Fernandez, Elisabet (Institut de Recerca i Tecnologia Agroalimentàries. Centre de Recerca en Sanitat Animal)
Bosch Camós, Laia (Institut de Recerca i Tecnologia Agroalimentàries. Centre de Recerca en Sanitat Animal)
Ramirez-Medina, Elizabeth (USDA Plum Island Animal Disease Center. Agricultural Research Service)
Vuono, Elizabeth (USDA Plum Island Animal Disease Center, Agricultural Research Service)
Navas, María Jesús (Institut de Recerca i Tecnologia Agroalimentàries. Centre de Recerca en Sanitat Animal)
Muñoz, Marta (Institut de Recerca i Tecnologia Agroalimentàries. Centre de Recerca en Sanitat Animal)
Accensi Alemany, Francesc (Universitat Autònoma de Barcelona. Departament de Sanitat i d'Anatomia Animals)
Zhang, Jinya (Institut de Recerca i Tecnologia Agroalimentàries. Centre de Recerca en Sanitat Animal)
Alonso, Uxía (Institut de Recerca i Tecnologia Agroalimentàries. Centre de Recerca en Sanitat Animal)
Argilaguet, Jordi 1977- (Institut de Recerca i Tecnologia Agroalimentàries. Centre de Recerca en Sanitat Animal)
Salas, Maria Luisa (Centro de Biología Molecular Severo Ochoa)
Anachkov, Nikolay (Biologics Development, Huvepharmaa)
Gladue, Douglas P. (USDA Plum Island Animal Disease Center. Agricultural Research Service)
Borca, Manuel V. (USDA Plum Island Animal Disease Center. Agricultural Research Service)
Pina-Pedrero, Sonia (Institut de Recerca i Tecnologia Agroalimentàries. Centre de Recerca en Sanitat Animal)
Rodriguez, Fernando (Institut de Recerca i Tecnologia Agroalimentàries. Centre de Recerca en Sanitat Animal)

Date:	2021
Abstract:	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 f, 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 f, BA71∆CD2DP96R and BA71∆CD2EP153R recombinant viruses as immunogens, demonstrated that deletion of either DP96R or EP153R from BA71∆CD2 f 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.
Grants:	Ministerio de Ciencia, Innovación y Universidades AGL2016-78160-C2-1-R
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	African swine fever (ASF) ; African swine fever virus (ASFV) ; Live attenuated virus (LAV) ; Vaccine ; Virulence factor ; Double mutant ; Protection
Published in:	Viruses, Vol. 13 (august 2021) , ISSN 1999-4915

DOI: 10.3390/v13091678
PMID: 34578263

13 p, 1.7 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Centre de Recerca en Sanitat Animal (CReSA-IRTA)
Articles > Research articles
Articles > Published articles