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      Bovine Herpesvirus-4-Based Vector Delivering Peste des Petits Ruminants Virus Hemagglutinin ORF Induces both Neutralizing Antibodies and Cytotoxic T Cell Responses

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          Abstract

          Peste des Petits Ruminants Virus (PPRV) is an extremely infective morbillivirus that primarily affects goats and sheep. In underdeveloped countries where livestock are the main economical resource, PPRV causes considerable economic losses. Protective live attenuated vaccines are currently available but they induce antibody responses similar to those produced in PPRV naturally infected animals. Effective vaccines able to distinguish between vaccinated and naturally infected animals are required to PPRV control and eradication programs. Hemagglutinin (H) is a highly immunogenic PPRV envelope glycoprotein displaying both hemagglutinin and neuraminidase activities, playing a crucial role in virus attachment and penetration. In this study, a recombinant Bovine Herpesvirus-4 (BoHV-4)-based vector delivering an optimized PPRV-Hemagglutinin expression cassette, BoHV-4-A-PPRV-H-ΔTK, was assessed in immunocompetent C57BL/6 mice. BoHV-4-A-PPRV-H-ΔTK-immunization elicited both cellular and humoral immune responses with specific T cell, cytotoxic T lymphocyte, and sero-neutralizing antibody against PPRV. These data suggest recombinant BoHV-4-A-PPRV-H-ΔTK as an effective vaccine candidate to protect against PPRV herd infection and potentially applicable for eradication programs.

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          The threat of peste des petits ruminants: progress in vaccine development for disease control.

          Peste des petits ruminants (PPR) is a highly contagious animal disease caused by a virus in the genus Morbillivirus, family Paramyxoviridae. This infection is responsible for high morbidity and mortality in sheep and goats and in some small wild ruminant species. The huge number of small ruminants, which are reared in the endemic areas makes PPR a serious disease threatening the livelihood of poor farmers. Taking advantage of the closely relationship between rinderpest and PPR viruses, the attenuated rinderpest vaccine was used in the control of PPR. It is now replaced by the homologous attenuated PPR vaccine. Unfortunately, animals that have received this vaccine cannot be distinguished serologically from infected animals. With the advent of DNA recombinant technology, efforts are being made to develop effective PPR marker vaccines to enable such differentiation and which would allow countries to implement both vaccination and disease surveillance programmes at the same time.
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            Peste des Petits Ruminants Virus.

            Peste des petits ruminants virus (PPRV) causes a severe contagious disease of sheep and goats and has spread extensively through the developing world. Because of its disproportionately large impact on the livelihoods of low-income livestock keepers, and the availability of effective vaccines and good diagnostics, the virus is being targeted for global control and eventual eradication. In this review we examine the origin of the virus and its current distribution, and the factors that have led international organizations to conclude that it is eradicable. We also review recent progress in the molecular and cellular biology of the virus and consider areas where further research is required to support the efforts being made by national, regional, and international bodies to tackle this growing threat.
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              Development of a DIVA (Differentiating Infected from Vaccinated Animals) strategy using a vaccine containing a heterologous neuraminidase for the control of avian influenza.

              The present paper reports of the development and validation of a control strategy for avian influenza infections in poultry. The "DIVA" (Differentiating Infected from Vaccinated Animals) strategy is based on the use of an inactivated oil emulsion vaccine containing the same haemagglutinin (H) subtype as the challenge virus, but a different neuraminidase (N). The possibility of using the heterologous N subtype, to differentiate between vaccinated and naturally infected birds, was investigated through the development of an "ad hoc" serological test based on the detection of specific anti-N1 antibodies. This was achieved using a baculovirus expressing a recombinant N1 protein. The A/ck/Pakistan/H7N3 virus was used as a vaccine and birds were challenged with the HPAI A/ty/Italy/4580/V99/H7N1 strain. The homologous H group ensured a clinical protection of 93% regardless of the vaccination scheme used, and was able to prevent viraemia and muscle colonization in the clinically healthy challenged birds. However, it was not able to prevent viral shedding. The "ad hoc" serological assay was developed as an indirect immunofluorescence test, and was validated using 608 field sera, and showed an "almost perfect agreement" (Kappa value) with the HI test, with relative sensitivity and specificity values of 98.1 and 95.7, respectively. The results of the present investigation suggest that the "DIVA" control strategy may represent a tool for the control of avian influenza infections in poultry.
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                Author and article information

                Contributors
                URI : http://frontiersin.org/people/u/531025
                URI : http://frontiersin.org/people/u/523081
                URI : http://frontiersin.org/people/u/44975
                URI : http://frontiersin.org/people/u/524923
                URI : http://frontiersin.org/people/u/391512
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                05 March 2018
                2018
                : 9
                : 421
                Affiliations
                [1] 1Department of Medical Veterinary Science, University of Parma , Parma, Italy
                [2] 2Centro de Investigación en Sanidad Animal (CISA-INIA), Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria , Madrid, Spain
                Author notes

                Edited by: Fabrizio Ceciliani, Università degli Studi di Milano, Italy

                Reviewed by: Simon Paul Graham, Pirbright Institute (BBSRC), United Kingdom; Martin Faldyna, Veterinary Research Institute (VRI), Czechia

                *Correspondence: Gaetano Donofrio, gaetano.donofrio@ 123456unipr.it

                Specialty section: This article was submitted to Comparative Immunology, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2018.00421
                5845008
                29556236
                f6df6d4d-1ece-44a5-a10d-316c4c93ed4d
                Copyright © 2018 Macchi, Rojas, Verna, Sevilla, Franceschi, Tebaldi, Cavirani, Martín and Donofrio.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 11 January 2018
                : 15 February 2018
                Page count
                Figures: 4, Tables: 1, Equations: 0, References: 53, Pages: 11, Words: 7306
                Categories
                Immunology
                Original Research

                Immunology
                bohv-4,pprv,diva vaccines,h antigen,viral vaccines
                Immunology
                bohv-4, pprv, diva vaccines, h antigen, viral vaccines

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