Vaccine 30 (2012) 1609–1616 Contents lists available at SciVerse ScienceDirect Vaccine jou rn al h om epa ge: www.elsevier.com/locate/vaccine Myxomavirus as a vector for the immunisation of sheep: Protection study against challenge with bluetongue virus Sokunthea Top a , Gilles Foucras b,a , Martine Deplanche a , Germain Rives b , Jérôme Calvalido b , Loic Comtet c , Stéphane Bertagnoli b,a , Gilles Meyer b,a,∗ a INRA, UMR1225, IHAP, F-31076 Toulouse, France b Université de Toulouse, INP, ENVT, UMR1225, IHAP, F-31076 Toulouse, France c ID VET, 167 rue Mehdi Ben Barka - Zone Garosud, F-34070 Montpellier, France a r t i c l e i n f o Article history: Received 28 October 2011 Received in revised form 15 December 2011 Accepted 22 December 2011 Available online 13 January 2012 Keywords: Myxomavirus Sheep Immunisation Bluetongue a b s t r a c t Recombinant poxviruses are well suited for the development of new vaccine vectors. Our previous data supported the idea that Myxomavirus (MYXV) is efficient at priming antibody responses in sheep. To provide definitive evidence on the potential of MYXV for vaccination against infectious diseases in rumi- nants, we investigated the immune protection provided by recombinant MYXV against bluetongue, a devastating disease in sheep. To test this concept, sheep were injected twice with an MYXV express- ing the immunodominant VP2 protein (SG33-VP2). The SG33-VP2 vector promoted the production of neutralising antibodies and partially protected sheep against disease after challenge with a highly viru- lent strain of serotype-8 bluetongue virus (BTV-8). In contrast, an MYXV expressing both VP2 and VP5 proteins (SG33-VP2/5) elicited very little protection. The expression levels of the VP2 and VP5 proteins suggested that, greater than the co-expression of the VP5 protein which was previously thought to favour anti-VP2 antibody response, the high expression of VP2 may be critical in the MYXV context to stimu- late a protective response in sheep. This highlights the requirement for a careful examination of antigen expression before any conclusion can be drawn on the respective role of the protective antigens. As a proof of principle, our study shows that an MYXV vaccine vector is possible in ruminants. © 2011 Elsevier Ltd. All rights reserved. 1. Introduction The development of new vaccines using recombinant poxviruses has been well documented [1,2] as these viruses combine both safety and strong immunogenicity [3]. Several poxvirus vectors are currently under evaluation for vaccine development against infectious diseases [4–8]. Vaccinia virus (VACV) has been the most extensively studied poxvirus vector; however, concern over broad host-range specificity and risks to immuno-compromised persons has led to the search for alterna- tive poxviruses. In ruminants, both replicative capripoxvirus and non-replicative modified vaccine Ankara (MVA) or avipoxvirus vectors have been used with some success for immunisation against livestock diseases [9,10]. One advantage of these vectors is that they make it possible to distinguish naturally infected animals from vaccinated animals (DIVA strategy) in control programmes. ∗ Corresponding author at: Université de Toulouse, INP, ENVT, UMR1225, IHAP, F-31076 Toulouse, France. Tel.: +33 561 193 298; fax: +33 561 193 834. E-mail address: g.meyer@envt.fr (G. Meyer). During the last few years, we investigated the potential of Myxomavirus (MYXV) to be used as a non-replicative vector for ruminant immunisation. We have previously shown that MYXV can abortively infect several ruminant cell types, such as peripheral blood mononuclear cells (PBMCs) [11] and bone marrow-derived dendritic cells (BoM-DCs) [12], and that it permits recombinant antigen expression. Gene expression arrays of MYXV-infected ovine BoM-DCs indicated a strong up-regulation of type I IFN- related genes and expression of a set of genes regulated by IRF7 that were previously shown to be predictive for vaccine efficacy [12]. In parallel, in vivo studies showed that MYXV is safe in sheep and that it can induce a humoral immune response against a recom- binant protein with biological relevance [11,13]. Collectively, these data support the idea that MYXV should be considered a promising vector amongst poxviruses. To provide definitive evidence on the potential of MYXV for vac- cination in ruminants, in this study, we investigated the capacity of the MYXV SG33 vaccine strain to provide immune protection against a major infectious disease in sheep. To this end, we used a challenge with a highly virulent bluetongue serotype 8 (BTV-8) isolate. Several poxvirus-based recombinant vaccines have previ- ously been tested in a BTV challenge [10,14,15]. These studies used 0264-410X/$ – see front matter © 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.vaccine.2011.12.108