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      Protection of European domestic pigs from virulent African isolates of African swine fever virus by experimental immunisation

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          Abstract

          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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          Most cited references26

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          Comparison of the genome sequences of non-pathogenic and pathogenic African swine fever virus isolates.

          The genomic coding sequences, apart from the inverted terminal repeats and cross-links, have been determined for two African swine fever virus (ASFV) isolates from the same virus genotype, a non-pathogenic isolate from Portugal, OURT88/3, and a highly pathogenic isolate from West Africa, Benin 97/1. These genome sequences were annotated and compared with that of a tissue culture-adapted isolate, BA71V. The genomes range in length between 170 and 182 kbp and encode between 151 and 157 open reading frames (ORFs). Compared to the Benin 97/1 isolate, the OURT88/3 and BA71V isolates have deletions of 8-10 kbp that encode six copies of the multigene family (MGF) 360 and either one MGF 505/530 copy in the BA71V or two copies in the OURT88/3 isolate. The BA71V isolate has a deletion, close to the right end of the genome, of 3 kbp compared with the other isolates. The five ORFs in this region include an additional copy of an ORF similar to that encoding the p22 virus structural protein. The OURT88/3 isolate has interruptions in ORFs that encode a CD2-like and a C-type lectin protein. Variation between the genomes is observed in the number of copies of five different MGFs. The 109 non-duplicated ORFs conserved in the three genomes encode proteins involved in virus replication, virus assembly and modulation of the host's defences. These results provide information concerning the genetic variability of African swine fever virus isolates that differ in pathogenicity.
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            The non-haemadsorbing African swine fever virus isolate ASFV/NH/P68 provides a model for defining the protective anti-virus immune response.

            African swine fever virus ASFV/NH/P68 is a naturally occurring, non-haemadsorbing and non-fatal isolate. Longitudinal clinical and immunological studies on 31 pigs inoculated oronasally or intramuscularly with this isolate defined two discrete groups of animals: those developing ASF chronic type lesions and those remaining asymptomatic. Animals developing lesions had viraemia and fever late after infection, NK activity levels close to that of control animals and high levels of anti-ASFV specific antibodies together with a marked hypergammaglobulinaemia involving IgG1, IgG2, IgM and IgA immunoglobulin isotypes. Pigs remaining asymptomatic after infection, on the other hand, did not have viraemia or fever after day 14 post-infection and had elevated NK cell activity, but normal plasma Ig concentrations and relatively low specific anti-virus antibody concentrations throughout the duration of the experiments. Importantly, the latter group of pigs virus were resistant to subsequent challenge with the highly virulent ASFV/L60 isolate and survived with no major changes in any of the parameters examined and referred to above. Finally, lymphoproliferative responses to the mitogens concanavalin A, phytohaemagglutinin and pokeweed mitogen were not depressed in either of the two clinically defined groups of pigs. Thus further studies with this infection model may provide new insights on mechanisms of protective immunity to ASFV.
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              In vivo depletion of CD8+ T lymphocytes abrogates protective immunity to African swine fever virus.

              To understand the mechanisms involved in protective immunity to African swine fever virus (ASFV) infection, the observation that infection with the avirulent Portuguese ASFV isolate OUR/T88/3 protects outbred pigs from challenge with the virulent Portuguese ASFV isolate OUR/T88/1 was exploited. It was demonstrated that pigs exposed to OUR/T88/3 and then depleted of CD8+ lymphocytes were no longer fully protected from OUR/T88/1 challenge. This indicated that CD8+ lymphocytes play an important role in the protective immune response to ASFV infection and that anti-ASFV antibody alone, from OUR/T88/3 infection, was not sufficient to protect pigs from OUR/T88/1 challenge. Inbred pigs of the cc haplotype infected with OUR/T88/3 were not always protected from OUR/T88/1 challenge and developed both viraemia and fever. Such viraemia was always correlated with increased numbers of circulating CD8beta+ lymphocytes, indicating a specific role for CD8beta+ lymphocytes in combating viraemia. These experiments indicate an important role for CD8+ lymphocytes, particularly CD8beta+ lymphocytes, in ASF protective immunity.

                Author and article information

                Journal
                Vaccine
                Vaccine
                Vaccine
                Elsevier Science
                0264-410X
                1873-2518
                20 June 2011
                20 June 2011
                : 29
                : 28
                : 4593-4600
                Affiliations
                [a ]Institute for Animal Health Pirbright Laboratory, Pirbright, Woking, Surrey GU24 0NF, UK
                [b ]Royal Veterinary College, University of London, Hatfield, Hertfordshire AL9 7TA, UK
                [c ]Centre de Recerca en Sanitat Animal, Campus de la UAB, Barcelona, Spain/Biologia de la Infecció, CEXS, Universitat Pompeu Fabra, Barcelona, Spain
                [d ]Anses, Laboratoire de Ploufragan, Unité Virologie Immunologie Porcines, Zoopôle Les Croix, B.P. 53, 22440 Ploufragan, France
                Author notes
                [* ]Corresponding authors. Tel.: +44 0 1483 232 441; fax: +44 0 1483 232 448. linda.dixon@ 123456bbsrc.ac.uk haru.takamatsu@ 123456bbsrc.ac.uk
                Article
                JVAC11725
                10.1016/j.vaccine.2011.04.052
                3120964
                21549789
                c9be6e0f-5ec4-40e9-86a0-66d487e1b720
                © 2011 Elsevier Ltd.

                This document may be redistributed and reused, subject to certain conditions.

                History
                : 4 February 2011
                : 8 April 2011
                : 17 April 2011
                Categories
                Article

                Infectious disease & Microbiology
                immunisation,protection,african swine fever,pigs,asfarviridae
                Infectious disease & Microbiology
                immunisation, protection, african swine fever, pigs, asfarviridae

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