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      BA71ΔCD2: a New Recombinant Live Attenuated African Swine Fever Virus with Cross-Protective Capabilities

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          ABSTRACT

          African swine fever is a highly contagious viral disease of mandatory declaration to the World Organization for Animal Health (OIE). The lack of available vaccines makes its control difficult; thus, African swine fever virus (ASFV) represents a major threat to the swine industry. Inactivated vaccines do not confer solid protection against ASFV. Conversely, live attenuated viruses (LAV), either naturally isolated or obtained by genetic manipulation, have demonstrated reliable protection against homologous ASFV strains, although little or no protection has been demonstrated against heterologous viruses. Safety concerns are a major issue for the use of ASFV attenuated vaccine candidates and have hampered their implementation in the field so far. While trying to develop safer and efficient ASFV vaccines, we found that the deletion of the viral CD2v (EP402R) gene highly attenuated the virulent BA71 strain in vivo. Inoculation of pigs with the deletion mutant virus BA71ΔCD2 conferred protection not only against lethal challenge with the parental BA71 but also against the heterologous E75 (both genotype I strains). The protection induced was dose dependent, and the cross-protection observed in vivo correlated with the ability of BA71ΔCD2 to induce specific CD8 + T cells capable of recognizing both BA71 and E75 viruses in vitro. Interestingly, 100% of the pigs immunized with BA71ΔCD2 also survived lethal challenge with Georgia 2007/1, the genotype II strain of ASFV currently circulating in continental Europe. These results open new avenues to design ASFV cross-protective vaccines, essential to fight ASFV in areas where the virus is endemic and where multiple viruses are circulating.

          IMPORTANCE African swine fever virus (ASFV) remains enzootic in most countries of Sub-Saharan Africa, today representing a major threat for the development of their swine industry. The uncontrolled presence of ASFV has favored its periodic exportation to other countries, the last event being in Georgia in 2007. Since then, ASFV has spread toward neighboring countries, reaching the European Union's east border in 2014. The lack of available vaccines against ASFV makes its control difficult; so far, only live attenuated viruses have demonstrated solid protection against homologous experimental challenges, but they have failed at inducing solid cross-protective immunity against heterologous viruses. Here we describe a new LAV candidate with unique cross-protective abilities: BA71ΔCD2. Inoculation of BA71ΔCD2 protected pigs not only against experimental challenge with BA71, the virulent parental strain, but also against heterologous viruses, including Georgia 2007/1, the genotype II strain of ASFV currently circulating in Eastern Europe.

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          A5-miseq: an updated pipeline to assemble microbial genomes from Illumina MiSeq data.

          Open-source bacterial genome assembly remains inaccessible to many biologists because of its complexity. Few software solutions exist that are capable of automating all steps in the process of de novo genome assembly from Illumina data.
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            A statistical framework for SNP calling, mutation discovery, association mapping and population genetical parameter estimation from sequencing data

            (2013)
            Motivation: Most existing methods for DNA sequence analysis rely on accurate sequences or genotypes. However, in applications of the next-generation sequencing (NGS), accurate genotypes may not be easily obtained (e.g. multi-sample low-coverage sequencing or somatic mutation discovery). These applications press for the development of new methods for analyzing sequence data with uncertainty. Results: We present a statistical framework for calling SNPs, discovering somatic mutations, inferring population genetical parameters and performing association tests directly based on sequencing data without explicit genotyping or linkage-based imputation. On real data, we demonstrate that our method achieves comparable accuracy to alternative methods for estimating site allele count, for inferring allele frequency spectrum and for association mapping. We also highlight the necessity of using symmetric datasets for finding somatic mutations and confirm that for discovering rare events, mismapping is frequently the leading source of errors. Availability: http://samtools.sourceforge.net. Contact: hengli@broadinstitute.org.
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              Protection of European domestic pigs from virulent African isolates of African swine fever virus by experimental immunisation

              African swine fever (ASF) is an acute haemorrhagic disease of domestic pigs for which there is currently no vaccine. We showed that experimental immunisation of pigs with the non-virulent OURT88/3 genotype I isolate from Portugal followed by the closely related virulent OURT88/1 genotype I isolate could confer protection against challenge with virulent isolates from Africa including the genotype I Benin 97/1 isolate and genotype X Uganda 1965 isolate. This immunisation strategy protected most pigs challenged with either Benin or Uganda from both disease and viraemia. Cross-protection was correlated with the ability of different ASFV isolates to stimulate immune lymphocytes from the OURT88/3 and OURT88/1 immunised pigs.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                J Virol
                J. Virol
                jvi
                jvi
                JVI
                Journal of Virology
                American Society for Microbiology (1752 N St., N.W., Washington, DC )
                0022-538X
                1098-5514
                16 August 2017
                13 October 2017
                1 November 2017
                13 October 2017
                : 91
                : 21
                : e01058-17
                Affiliations
                [a ]IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB), Campus de la Universitat Autònoma de Barcelona, Bellaterra, Spain
                [b ]UAB, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB), Campus de la Universitat Autònoma de Barcelona, Bellaterra, Spain
                [c ]Departament de Sanitat i Anatomia Animals, Facultat de Veterinària, UAB, Bellaterra, Barcelona, Spain
                [d ]Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas and Universidad Autònoma de Madrid, Madrid, Spain
                [e ]Centro Nacional de Microbiología (ISCIII), Majadahonda, Madrid, Spain
                [f ]Boehringer Ingelheim Veterinary Research Center GmbH & Co. KG, Hannover, Germany
                University of Southern California
                Author notes
                Address correspondence to Fernando Rodríguez, fernando.rodriguez@ 123456irta.cat .

                M.L.S. and F.R. contributed equally to this article.

                Citation Monteagudo PL, Lacasta A, López E, Bosch L, Collado J, Pina-Pedrero S, Correa-Fiz F, Accensi F, Navas MJ, Vidal E, Bustos MJ, Rodríguez JM, Gallei A, Nikolin V, Salas ML, Rodríguez F. 2017. BA71ΔCD2: a new recombinant live attenuated African swine fever virus with cross-protective capabilities. J Virol 91:e01058-17. https://doi.org/10.1128/JVI.01058-17.

                Article
                01058-17
                10.1128/JVI.01058-17
                5640839
                28814514
                285888bc-2386-43b7-bb3e-795c654ade44
                Copyright © 2017 Monteagudo et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

                History
                : 28 June 2017
                : 7 August 2017
                Page count
                Figures: 8, Tables: 2, Equations: 0, References: 77, Pages: 17, Words: 11071
                Funding
                Funded by: Ministerio de Economía y Competitividad (MINECO) https://doi.org/10.13039/501100003329
                Award ID: AGL2013-48998-C2-1-R
                Award ID: AGL2013-48998-C2-2-R
                Award ID: AGL2016-78160-C2-1-R.
                Award Recipient : Paula López Monteagudo Award Recipient : Anna Lacasta Award Recipient : Elisabeth López Award Recipient : Laia Bosch Award Recipient : Javier Collado Award Recipient : Sonia Pina-Pedrero Award Recipient : Florencia Correa-Fiz Award Recipient : Francesc Accensi Award Recipient : María Jesús Navas Award Recipient : María J. Bustos Award Recipient : María L. Salas Award Recipient : Fernando Rodríguez
                Categories
                Vaccines and Antiviral Agents
                Custom metadata
                November 2017

                Microbiology & Virology
                african swine fever virus,cd8 t cells,cross-protection,live attenuated virus,vaccine

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