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      Efficacy of three innovative bacterin vaccines against experimental infection with Mycoplasma hyopneumoniae

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          Abstract

          New vaccine formulations that include novel strains of Mycoplasma hyopneumoniae and innovative adjuvants designed to induce cellular immunity could improve vaccine efficacy against this pathogen. The aim of this experimental study was to assess the efficacy of three experimental bacterin formulations based on M. hyopneumoniae field strain F7.2C which were able to induce cellular immunity. The formulations included a cationic liposome formulation with the Mincle receptor ligand trehalose 6,6-dibehenate (Lipo_DDA:TDB), a squalene-in-water emulsion with Toll-like receptor (TLR) ligands targeting TLR1/2, TLR7/8 and TLR9 (SWE_TLR), and a poly(lactic- co-glycolic acid) micro-particle formulation with the same TLR ligands (PLGA_TLR). Four groups of 12  M. hyopneumoniae-free piglets were primo- (day (D) 0; 39 days of age) and booster vaccinated (D14) intramuscularly with either one of the three experimental bacterin formulations or PBS. The pigs were endotracheally inoculated with a highly and low virulent M. hyopneumoniae strain on D28 and D29, respectively, and euthanized on D56. The main efficacy parameters were: respiratory disease score (RDS; daily), macroscopic lung lesion score (D56) and log copies M. hyopneumoniae DNA determined with qPCR on bronchoalveolar lavage (BAL) fluid (D42, D56). All formulations were able to reduce clinical symptoms, lung lesions and the M. hyopneumoniae DNA load in the lung, with formulation SWE_TLR being the most effective (RDS D28–D56 −61.90%, macroscopic lung lesions −88.38%, M. hyopneumoniae DNA load in BAL fluid (D42) −67.28%). Further experiments raised under field conditions are needed to confirm these results and to assess the effect of the vaccines on performance parameters.

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          Migration, maintenance and recall of memory T cells in peripheral tissues.

          After the resolution of an immune response, antigen-specific memory T cells persist at many sites in the body. The antigen-specific memory T-cell pool includes memory T cells that preferentially reside in peripheral tissues, such as the skin, gut and lungs, where they provide a first line of defence against secondary pathogen infection. Determining how peripheral memory T cells are regulated is essential for our understanding of host-pathogen interactions and for vaccine development. In this Review, we discuss recent insights into the generation, control and recall of peripheral T-cell memory responses.
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            Control of Mycoplasma hyopneumoniae infections in pigs

            Mycoplasma hyopneumoniae, the primary pathogen of enzootic pneumonia, occurs worldwide and causes major economic losses to the pig industry. The organism adheres to and damages the ciliated epithelium of the respiratory tract. Affected pigs show chronic coughing, are more susceptible to other respiratory infections and have a reduced performance. Control of the disease can be accomplished in a number of ways. First, management practices and housing conditions in the herd should be optimized. These include all-in/all-out production, limiting factors that may destabilize herd immunity, maintaining optimal stocking densities, prevention of other respiratory diseases, and optimal housing and climatic conditions. Strategic medication with antimicrobials active against M. hyopneumoniae and, preferably, also against major secondary bacteria may be useful during periods when the pigs are at risk for respiratory disease. Finally, commercial bacterins are widely used to control M. hyopneumoniae infections. The main effects of vaccination include less clinical symptoms, lung lesions and medication use, and improved performance. However, bacterins provide only partial protection and do not prevent colonization of the organism. Different vaccination strategies (timing of vaccination, vaccination of sows, vaccination combined with antimicrobial medication) can be used, depending on the type of herd, the production system and management practices, the infection pattern and the preferences of the pig producer. Research on new vaccines is actively occurring, including aerosol and feed-based vaccines as well as subunit and DNA vaccines. Eradication of the infection at herd level based on age-segregation and medication is possible, but there is a permanent risk for re-infections.
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              Update on Mycoplasma hyopneumoniae infections in pigs: Knowledge gaps for improved disease control.

              Mycoplasma hyopneumoniae (M. hyopneumoniae) is the primary pathogen of enzootic pneumonia, a chronic respiratory disease in pigs. Infections occur worldwide and cause major economic losses to the pig industry. The present paper reviews the current knowledge on M. hyopneumoniae infections, with emphasis on identification and analysis of knowledge gaps for optimizing control of the disease. Close contact between infected and susceptible pigs is the main route of M. hyopneumoniae transmission. Management and housing conditions predisposing for infection or disease are known, but further research is needed to better understand M. hyopneumoniae transmission patterns in modern pig production systems, and to assess the importance of the breeding population for downstream disease control. The organism is primarily found on the mucosal surface of the trachea, bronchi and bronchioles. Different adhesins and lipoproteins are involved in the adherence process. However, a clear picture of the virulence and pathogenicity of M. hyopneumoniae is still missing. The role of glycerol metabolism, myoinositol metabolism and the Mycoplasma Ig binding protein-Mycoplasma Ig protease system should be further investigated for their contribution to virulence. The destruction of the mucociliary apparatus, together with modulating the immune response, enhances the susceptibility of infected pigs to secondary pathogens. Clinical signs and severity of lesions depend on different factors, such as management, environmental conditions and likely also M. hyopneumoniae strain. The potential impact of strain variability on disease severity is not well defined. Diagnostics could be improved by developing tests that may detect virulent strains, by improving sampling in live animals and by designing ELISAs allowing discrimination between infected and vaccinated pigs. The currently available vaccines are often cost-efficient, but the ongoing research on developing new vaccines that confer protective immunity and reduce transmission should be continued, as well as optimization of protocols to eliminate M. hyopneumoniae from pig herds.
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                Author and article information

                Contributors
                Anneleen.Matthijs@ugent.be
                gael.auray@ivi.admin.ch
                Filip.Boyen@ugent.be
                Alexandra.Schoos@ugent.be
                Annelies.Michiels@ugent.be
                obdulio.garcia-nicolas@ivi.admin.ch
                gueliz.barut@vetsuisse.unibe.ch
                barnierquer@gmail.com
                Virginie.Jakob@unil.ch
                nicolas.collin@unil.ch
                B.Devriendt@ugent.be
                Artur.Summerfield@ivi.admin.ch
                Freddy.Haesebrouck@ugent.be
                Dominiek.Maes@ugent.be
                Journal
                Vet Res
                Vet. Res
                Veterinary Research
                BioMed Central (London )
                0928-4249
                1297-9716
                8 November 2019
                8 November 2019
                2019
                : 50
                : 91
                Affiliations
                [1 ]ISNI 0000 0001 2069 7798, GRID grid.5342.0, Department of Reproduction, Obstetrics and Herd Health, Faculty of Veterinary Medicine, , Ghent University, ; Salisburylaan 133, 9820 Merelbeke, Belgium
                [2 ]Institute of Virology and Immunology, Sensemattstrasse 293, 3147 Mittelhäusern, Switzerland
                [3 ]ISNI 0000 0001 0726 5157, GRID grid.5734.5, Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, , University of Bern, ; Länggassstrasse 120, 3012 Bern, Switzerland
                [4 ]ISNI 0000 0001 2069 7798, GRID grid.5342.0, Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, , Ghent University, ; Salisburylaan 133, 9820 Merelbeke, Belgium
                [5 ]ISNI 0000 0001 2165 4204, GRID grid.9851.5, Vaccine Formulation Laboratory, , University of Lausanne, ; Chemin des Boveresses 155, 1066 Epalinges, Switzerland
                [6 ]ISNI 0000 0001 2069 7798, GRID grid.5342.0, Laboratory of Veterinary Immunology, Department of Virology, Parasitology and Immunology, Faculty of Veterinary Medicine, , Ghent University, ; Salisburylaan 133, 9820 Merelbeke, Belgium
                Author information
                http://orcid.org/0000-0003-2020-1726
                Article
                709
                10.1186/s13567-019-0709-0
                6842239
                31703726
                41f681d9-5f88-4b4a-b8b2-b4e7ab61777e
                © The Author(s) 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 14 June 2019
                : 25 September 2019
                Funding
                Funded by: European H2020 Project SAPHIR (Project No. 633184)
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2019

                Veterinary medicine
                Veterinary medicine

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