Research Center en Sanidad Animal

Valdeolmos, Spain

Research Center en Sanidad Animal

Valdeolmos, Spain
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Ballester M.,Autonomous University of Barcelona | Rodriguez-Carino C.,Autonomous University of Barcelona | Perez M.,Autonomous University of Barcelona | Gallardo C.,Research Center en Sanidad Animal | And 3 more authors.
Journal of Virology | Year: 2011

African swine fever virus (ASFV), the causative agent of one of the most devastating swine diseases, has been considered exclusively cytoplasmic, even though some authors have shown evidence of an early stage of nuclear replication. In the present study, an increment of lamin A/C phosphorylation was observed in ASFV-infected cells as early as 4 h postinfection, followed by the disassembling of the lamina network close to the sites where the viral genome starts its replication. At later time points, this and other nuclear envelope markers were found in the cytoplasm of the infected cells. The effect of the infection on the cell nucleus was much more severe than previously expected, since a redistribution of other nuclear proteins, such as RNA polymerase II, the splicing speckle SC-35 marker, and the B-23 nucleolar marker, was observed from 4 h postinfection. All this evidence, together with the redistribution, dephosphorylation, and subsequent degradation of RNA polymerase II after ASFV infection, suggests the existence of sophisticated mechanisms to regulate the nuclear machinery during viral infection. © 2011, American Society for Microbiology.

Abos B.,Research Center en Sanidad Animal | Castro R.,Research Center en Sanidad Animal | Granja A.G.,Research Center en Sanidad Animal | Havixbeck J.J.,University of Alberta | And 2 more authors.
Journal of Virology | Year: 2015

To date, the response of teleost B cells to specific pathogens has been only scarcely addressed. In this work, we have demonstrated that viral hemorrhagic septicemia virus (VHSV), a fish rhabdovirus, has the capacity to infect rainbow trout spleen IgMpositive (IgM+) cells, although the infection is not productive. Consequently, we have studied the effects of VHSV on IgM+ cell functionality, comparing these effects to those elicited by a Toll-like receptor 3 (TLR3) ligand, poly(I·C). We found that poly(I·C) and VHSV significantly upregulated TLR3 and type I interferon (IFN) transcription in spleen and blood IgM+ cells. Further effects included the upregulated transcription of the CK5B chemokine. The significant inhibition of some of these effects in the presence of bafilomycin A1 (BAF), an inhibitor of endosomal acidification, suggests the involvement of an intracellular TLR in these responses. In the case of VHSV, these transcriptional effects were dependent on viral entry into B cells and the initiation of viral transcription. VHSV also provoked the activation of NF-κB and the upregulation of major histocompatibility complex class II (MHC-II) cell surface expression on IgM+ cells, which, along with the increased transcription of the costimulatory molecules CD80/86 and CD83, pointed to VHSV-induced IgM+ cell activation toward an antigen-presenting profile. Finally, despite the moderate effects of VHSV on IgM+ cell proliferation, a consistent effect on IgM+ cell survival was detected. © 2015, American Society for Microbiology.

Tafalla C.,Research Center en Sanidad Animal | Bogwald J.,University of Tromsø | Dalmo R.A.,University of Tromsø
Fish and Shellfish Immunology | Year: 2013

Vaccination is the most adequate method to control infectious diseases that threaten the aquaculture industry worldwide. Unfortunately, vaccines are usually not able to confer protection on their own; especially those vaccines based on recombinant antigens or inactivated pathogens. Therefore, the use of adjuvants or immunostimulants is often necessary to increase the vaccine efficacy. Traditional adjuvants such as mineral oils are routinely used in different commercial bacterial vaccines available for fish; however, important side effects may occur with this type of adjuvants. A search for alternative molecules or certain combinations of them as adjuvants is desirable in order to increase animal welfare without reducing protection levels. Especially, combinations that may target specific cell responses and thus a specific pathogen, with no or minor side effects, should be explored. Despite this, the oil adjuvants currently used are quite friendlier with respect to side effects compared with the oil adjuvants previously used. The great lack of fish antiviral vaccines also evidences the importance of identifying optimal combinations of a vaccination strategy with the use of a targeting adjuvant, especially for the promising fish antiviral DNA vaccines. In this review, we summarise previous studies performed with both traditional adjuvants as well as the most promising new generation adjuvants such as ligands for Toll receptors or different cytokines, focussing mostly on their protective efficacies, and also on what is known concerning their effects on the fish immune system when delivered invivo. © 2013 Elsevier Ltd.

Calvo-Pinilla E.,Research Center en Sanidad Animal | Navasa N.,University of Massachusetts Amherst | Anguita J.,University of Massachusetts Amherst | Ortego J.,Research Center en Sanidad Animal
PLoS ONE | Year: 2012

Bluetongue virus (BTV) belongs to the genus Orbivirus within the family Reoviridae. The development of vector-based vaccines expressing conserved protective antigens results in increased immune activation and could reduce the number of multiserotype vaccinations required, therefore providing a cost-effective product. Recent recombinant DNA technology has allowed the development of novel strategies to develop marker and safe vaccines against BTV. We have now engineered naked DNAs and recombinant modified vaccinia virus Ankara (rMVA) expressing VP2, VP7 and NS1 proteins from BTV-4. IFNAR (-/-) mice inoculated with DNA/rMVA-VP2,-VP7-NS1 in an heterologous prime boost vaccination strategy generated significant levels of antibodies specific of VP2, VP7, and NS1, including those with neutralizing activity against BTV-4. In addition, vaccination stimulated specific CD8 + T cell responses against these three BTV proteins. Importantly, the vaccine combination expressing NS1, VP2 and VP7 proteins of BTV-4, elicited sterile protection against a lethal dose of homologous BTV-4 infection. Remarkably, the vaccine induced cross-protection against lethal doses of heterologous BTV-8 and BTV-1 suggesting that the DNA/rMVA-VP2,-VP7,-NS1 marker vaccine is a promising multiserotype vaccine against BTV. © 2012 Calvo-Pinilla et al.

Monso M.,University Pompeu Fabra | De La Torre B.G.,University Pompeu Fabra | Blanco E.,Research Center en Sanidad Animal | Moreno N.,Research Center en Sanidad Animal | Andreu D.,University Pompeu Fabra
Bioconjugate Chemistry | Year: 2013

Multimeric presentation, a well-proven way of enhancing peptide immunogenicity, has found substantial application in synthetic vaccine design. We have reported that a combination of four copies of a B-cell epitope with one of a T-cell epitope in a single branched construct results in a peptide vaccine conferring total protection against foot-and-mouth disease virus in swine, a natural host (Cubillos et al. (2008) J. Virol.82, 7223-7230). More recently, a downsized version of this prototype with only two copies of the B epitope has proven as effective as the tetravalent one in mice. Here we evaluate three approaches to bivalent platforms of this latter type, involving different chemistries for the conjugation of two B epitope peptides to a branching T epitope. Comparison of classical thioether, "reverse" thioether (Monsó et al. (2012) Org. Biomol. Chem. 10, 3116-3121) and thiol-ene conjugation chemistries in terms of synthetic efficiency clearly singles out the latter, maleimide-based strategy as most advantageous. We also examine how minor structural differences among the conjugates -including the N-or C-terminal attachment of the B epitope to the branching T epitope -bear on the immunogenicity of these vaccine candidates, with the maleimide-based conjugate again emerging as the most successful. © 2013 American Chemical Society.

Barcena J.,Research Center en Sanidad Animal
Sub-cellular biochemistry | Year: 2013

Virus-like particles (VLPs) are formed by viral structural proteins that, when overexpressed, spontaneously self-assemble into particles that are antigenically indistinguishable from infectious virus or subviral particles. VLPs are appealing as vaccine candidates because their inherent properties (i.e., virus-sized, multimeric antigens, highly organised and repetitive structure, not infectious) are suitable for the induction of safe and efficient humoral and cellular immune responses. VLP-based vaccines have already been licensed for human and veterinary use, and many more vaccine candidates are currently in late stages of evaluation. Moreover, the development of VLPs as platforms for foreign antigen display has further broadened their potential applicability both as prophylactic and therapeutic vaccines. This chapter provides an overview on the design and use of VLPs for the development of new generation vaccines.

Alejo A.,Research Center en Sanidad Animal | Tafalla C.,Research Center en Sanidad Animal
Developmental and Comparative Immunology | Year: 2011

Chemokines are chemoattractant cytokines defined by the presence of four conserved cysteine residues which in mammals can be divided into four subfamilies depending on the arrangement of the first two conserved cysteines in their sequence: CXC (α), CC (β), C and CX 3C classes.Evolutionarily, fish can be considered as an intermediate step between species which possess only innate immunity (invertebrates) and species with a fully developed acquired immune network such as mammals. Therefore, the functionality of their different immune cell types and molecules is sometimes also intermediate between innate and acquired responses. The first chemokine gene identified in a teleost was a rainbow trout (Oncorhynchus mykiss) chemokine designated as CK1 in 1998. Since then, many different chemokine genes have been identified in several fish species, but their role in homeostasis and immune response remains largely unknown. Extensive genomic duplication events and the fact that chemokines evolve more quickly than other immune genes, make it very difficult to establish true orthologues between fish and mammalian chemokines that would help us with the ascription of immune roles. In this review, we describe the current state of knowledge of chemokine biology in teleost fish, focusing mainly on which genes have been identified so far and highlighting the most important aspects of their expression regulation, due to the great lack of functional information available for them. As the number of chemokine genes begins to close down for some teleost species, there is an important need for functional assays that may elucidate the role of each of these molecules within the fish immune response. © 2011 Elsevier Ltd.

Ortego J.,Research Center en Sanidad Animal | De la Poza F.,Research Center en Sanidad Animal | Marin-Lopez A.,Research Center en Sanidad Animal
Virus Research | Year: 2014

Bluetongue is an arthropod-borne disease caused by a virus of the genus Orbivirus, the bluetongue virus (BTV), which affects ruminant livestock such as cattle, sheep, and goats and wild ruminants such as deer, and camelids. Recently, adult mice with gene knockouts of the interferon α/β receptor (IFNAR-/-) have been described as a model of lethal BTV infection. IFNAR(-/-) mice are highly susceptible to BTV-1, BTV-4 and BTV-8 infection when the virus is administered intravenously or subcutaneosuly. Disease progression and pathogenesis closely mimics signs of bluetongue disease in ruminants. In the present paper we review the studies where IFNAR(-/-) mice have been used as an animal model to study BTV transmission, pathogenesis, virulence, and protective efficacy of inactivated and new recombinant marker BTV vaccines. Furthermore, we report new data on protective efficacy of different strategies of BTV vaccination and also on induction of interferon α/β and proinflammatory immune responses in IFNAR(-/-) mice infected with BTV. © 2013 Elsevier B.V.

Boshra H.,Research Center en Sanidad Animal | Lorenzo G.,Research Center en Sanidad Animal | Rodriguez F.,Autonomous University of Barcelona | Brun A.,Research Center en Sanidad Animal
Vaccine | Year: 2011

Current vaccine candidates against Rift Valley fever virus (RVFV) incorporate the viral structural glycoproteins as antigens, since triggering antibody responses against them usually correlates with protection. Here, we have focused solely on the nucleoprotein of RVFV as a potential target for vaccine development. Previous studies in mouse models have already demonstrated that RVFV nucleoprotein can elicit partial protection when administered by means of a DNA vaccine or in recombinant, soluble, protein form. To determine whether this partially protective immune response could be augmented to a level comparable to DNA constructs encoding for RVFV glycoproteins, several targeting sequences were cloned adjacent to the RVFV nucleoprotein (N) gene. Immunization with a plasmid construct encoding for a ubiquitinated form of the viral nucleoprotein (pCMV-Ub-N) significantly increased the survival of IFNAR-/- mice following viral challenge to levels comparable with a recombinant DNA-vaccine encoding both RVFV glycoproteins. Mice immunized with pCMV-Ub-N also displayed higher levels of non-neutralizing anti-N antibodies and antigen-specific T-cell responses. This suggests a role for other cell mediated responses in protection against RVFV. These findings show the potential of RVFV N as a candidate antigen for vaccination, and present a new strategy in vaccine design against certain bunyaviruses, where glycoprotein variation may impede effective broad-based vaccination strategies. © 2011 Elsevier Ltd.

Calvo-Pinilla E.,Research Center en Sanidad Animal | Nieto J.M.,Research Center en Sanidad Animal | Ortego J.,Research Center en Sanidad Animal
Journal of General Virology | Year: 2010

The identification of transmission routes for bluetongue virus (BTV) is essential to improve the control of the disease. Although BTV is primarily transmitted by several species of Culicoides biting midges, there has been evidence of transplacental and oral transmission. We now report that IFNAR (-/-) mice are susceptible to oral infection by BTV-8. Viraemia, clinical manifestations and tissue lesions are similar to those in intravenously infected mice. In addition, we show that the oral cavity and oesophagus are susceptible to BTV infection and replication, suggesting that these organs are possible entry routes during BTV oral infection. © 2010 SGM.

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