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      A DNA Prime Immuno-Potentiates a Modified Live Vaccine against the Porcine Reproductive and Respiratory Syndrome Virus but Does Not Improve Heterologous Protection

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          Abstract

          The porcine reproductive and respiratory syndrome virus (PRRSV), an RNA virus inducing abortion in sows and respiratory disease in young pigs, is a leading infectious cause of economic losses in the swine industry. Modified live vaccines (MLVs) help in controlling the disease, but their efficacy is often compromised by the high genetic diversity of circulating viruses, leading to vaccine escape variants in the field. In this study, we hypothesized that a DNA prime with naked plasmids encoding PRRSV antigens containing conserved T-cell epitopes may improve the protection of MLV against a heterologous challenge. Plasmids were delivered with surface electroporation or needle-free jet injection and European strain-derived PRRSV antigens were targeted or not to the dendritic cell receptor XCR1. Compared to MLV-alone, the DNA-MLV prime- boost regimen slightly improved the IFNγ T-cell response, and substantially increased the antibody response against envelope motives and the nucleoprotein N. The XCR1-targeting of N significantly improved the anti-N specific antibody response. Despite this immuno-potentiation, the DNA-MLV regimen did not further decrease the serum viral load or the nasal viral shedding of the challenge strain over MLV-alone. Finally, the heterologous protection, achieved in absence of detectable effective neutralizing antibodies, was not correlated to the measured antibody or to the IFNγ T-cell response. Therefore, immune correlates of protection remain to be identified and represent an important gap of knowledge in PRRSV vaccinology. This study importantly shows that a naked DNA prime immuno-potentiates an MLV, more on the B than on the IFNγ T-cell response side, and has to be further improved to reach cross-protection.

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          Most cited references 46

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          Mapping of Brain Activity by Automated Volume Analysis of Immediate Early Genes.

          Understanding how neural information is processed in physiological and pathological states would benefit from precise detection, localization, and quantification of the activity of all neurons across the entire brain, which has not, to date, been achieved in the mammalian brain. We introduce a pipeline for high-speed acquisition of brain activity at cellular resolution through profiling immediate early gene expression using immunostaining and light-sheet fluorescence imaging, followed by automated mapping and analysis of activity by an open-source software program we term ClearMap. We validate the pipeline first by analysis of brain regions activated in response to haloperidol. Next, we report new cortical regions downstream of whisker-evoked sensory processing during active exploration. Last, we combine activity mapping with axon tracing to uncover new brain regions differentially activated during parenting behavior. This pipeline is widely applicable to different experimental paradigms, including animal species for which transgenic activity reporters are not readily available.
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            Porcine Reproductive and Respiratory Syndrome Virus (PRRSV): Pathogenesis and Interaction with the Immune System.

            This review addresses important issues of porcine reproductive and respiratory syndrome virus (PRRSV) infection, immunity, pathogenesis, and control. Worldwide, PRRS is the most economically important infectious disease of pigs. We highlight the latest information on viral genome structure, pathogenic mechanisms, and host immunity, with a special focus on immune factors that modulate PRRSV infections during the acute and chronic/persistent disease phases. We address genetic control of host resistance and probe effects of PRRSV infection on reproductive traits. A major goal is to identify cellular/viral targets and pathways for designing more effective vaccines and therapeutics. Based on progress in viral reverse genetics, host transcriptomics and genomics, and vaccinology and adjuvant technologies, we have identified new areas for PRRS control and prevention. Finally, we highlight the gaps in our knowledge base and the need for advanced molecular and immune tools to stimulate PRRS research and field applications.
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              Cutting edge: expression of XCR1 defines mouse lymphoid-tissue resident and migratory dendritic cells of the CD8α+ type.

              Subsets of dendritic cells (DCs) have been described according to their functions and anatomical locations. Conventional DC subsets are defined by reciprocal expression of CD11b and CD8α in lymphoid tissues (LT), and of CD11b and CD103 in non-LT (NLT). Spleen CD8α(+) and dermal CD103(+) DCs share a high efficiency for Ag cross-presentation and a developmental dependency on specific transcription factors. However, it is not known whether all NLT-derived CD103(+) DCs and LT-resident CD8α(+) DCs are similar despite their different anatomical locations. XCR1 was previously described as exclusively expressed on mouse spleen CD8α(+) DCs and human blood BDCA3(+) DCs. In this article, we showed that LT-resident CD8α(+) DCs and NLT-derived CD103(+) DCs specifically express XCR1 and are characterized by a unique transcriptional fingerprint, irrespective of their tissue of origin. Therefore, CD8α(+) DCs and CD103(+) DCs belong to a common DC subset which is unequivocally identified by XCR1 expression throughout the body.
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                Author and article information

                Journal
                Viruses
                Viruses
                viruses
                Viruses
                MDPI
                1999-4915
                25 June 2019
                June 2019
                : 11
                : 6
                Affiliations
                [1 ]VIM, INRA, Université Paris-Saclay, Domaine de Vilvert, 78350 Jouy-en-Josas, France; bernelin.cottet.cindy@ 123456hotmail.fr (C.B.-C.); celine.urien@ 123456inra.fr (C.U.); maxence.fretaud@ 123456inra.fr (M.F.); christelle.langevin@ 123456inra.fr (C.L.); luc.jouneau@ 123456inra.fr (L.J.); nicolas.bertho@ 123456inra.fr (N.B.)
                [2 ]VIM, EMERG’IN-Plateforme d’Infectiologie Expérimentale IERP, INRA, Domaine de Vilvert, 78352 Jouy-en-Josas, France
                [3 ]Laboratory of Virology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, B-9820 Merelbeke, Belgium; ivan.trus@ 123456gmail.com (I.T.); hans.nauwynck@ 123456ugent.be (H.N.)
                [4 ]GABI, INRA-AgroParisTech, Université Paris-Saclay, Domaine de Vilvert, 78350 Jouy-en-Josas, France; Fany.blanc@ 123456inra.fr (F.B.); jeanjacques.leplat@ 123456inra.fr (J.-J.L.)
                [5 ]Plate-Forme d’Infectiologie Expérimentale-PFIE-UE1277, Centre Val de Loire, INRA, 37380 Nouzilly, France; celine.barc@ 123456inra.fr (C.B.); olivier.boulesteix@ 123456inra.fr (O.B.); mickael.riou@ 123456inra.fr (M.R.)
                [6 ]Pharmajet, 400 Corporate Circle Suite N, Golden, CO 80401, USA; marilyn.dysart@ 123456pharmajet.com
                [7 ]Unité Virologie et Immunologie Porcines, Laboratoire de Ploufragan-Plouzané-Niort, Anses, BP 53, 22440 Ploufragan, France; sophie.mahe@ 123456anses.fr (S.M.); olivier.bourry@ 123456anses.fr (O.B.)
                [8 ]Vaccibody AS, Gaustadalleen 21, 0349 Oslo, Norway; estubsrud@ 123456vaccibody.com
                Author notes
                [†]

                Current address: BIOEPAR, Oniris, INRA, 44307 Nantes, France.

                viruses-11-00576
                10.3390/v11060576
                6631340
                31242645
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

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