{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T19:59:13Z","timestamp":1789156753647,"version":"build-2803163510"},"reference-count":39,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T00:00:00Z","timestamp":1767139200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"MSD Animal Health"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>Vaccination is a tool to control Lawsonia intracellularis (LI) in pigs. However, pigs may have co-infections that worsen clinical signs and lesions. The aim of this study was to characterize systemic and gut-mediated humoral and cell-mediated immune (CMI) responses in pigs vaccinated with a killed intramuscular LI vaccine and to analyze the impact of co-infection with Brachyspira hyodysenteriae (Bhyo) on the immune response. The study included eighty pigs and five study groups: V-CO (LI-vaccinated and co-infected with LI + Bhyo, n = 21), P-CO (placebo and co-infected with LI + Bhyo, n = 18), V-LI (LI-vaccinated and infected with LI, n = 21), P-LI (placebo and infected with LI, n = 12), and NC (negative control, placebo and non-challenged, n = 8). Parameters analyzed: fecal score and pathogen shedding), gross intestinal lesions, LI intestinal colonization (IHC), serum IgG, LI-specific IFN-\u03b3 production (ELISPOT), and immune cell subsets (flow cytometry) in blood, mesenteric lymph nodes, Peyer\u2019s patches, and intestinal epithelium. LI vaccination significantly reduced LI fecal shedding, intestinal colonization, and macroscopic lesions\u2014even under Bhyo co-infection. Vaccinated pigs had earlier and stronger serum IgG and IFN-\u03b3 responses. B cells seem to play an important role in the local immune response, and T regulatory cells apparently do not have a significant role in immunomodulation. This study contributes to a better understanding of LI immune response and can provide subtract for further research in the control of LI.<\/jats:p>","DOI":"10.3390\/ani16010114","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T13:30:52Z","timestamp":1767187852000},"page":"114","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Immune Response of Pigs Vaccinated Against Proliferative Enteropathy and Co-Infected with Lawsonia intracellularis and Brachyspira hyodysenteriae"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0844-0436","authenticated-orcid":false,"given":"Sarah","family":"Chagas","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, University of Minnesota, St. Paul, MN 55108, USA"},{"name":"Escola de Veterin\u00e1ria e Zootecnia, Universidade Federal de Goi\u00e1s, Goi\u00e2nia 74001-970, GO, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peyton","family":"Jensen","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, University of Minnesota, St. Paul, MN 55108, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliana","family":"Paladino","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, University of Minnesota, St. Paul, MN 55108, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00edvia Mendon\u00e7a","family":"Pascoal","sequence":"additional","affiliation":[{"name":"Escola de Veterin\u00e1ria e Zootecnia, Universidade Federal de Goi\u00e1s, Goi\u00e2nia 74001-970, GO, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"von Berg","sequence":"additional","affiliation":[{"name":"MSD Animal Health, 85716 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7066-9178","authenticated-orcid":false,"given":"Connie","family":"Gebhart","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, University of Minnesota, St. Paul, MN 55108, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio A.","family":"Vannucci","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, University of Minnesota, St. Paul, MN 55108, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Vannucci, F.A., Gebhart, C.J., and McOrist, S. (2019). Proliferative Enteropathy. Diseases of Swine, Wiley.","DOI":"10.1002\/9781119350927.ch58"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"127","DOI":"10.54846\/jshap\/346","article-title":"Monitoring the prevalence of Lawsonia intracellularis IgG antibodies using serial sampling in growing and breeding swine herds","volume":"11","author":"Marsteller","year":"2003","journal-title":"J. Swine Health Prod."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s40813-019-0137-6","article-title":"Prevalence of Lawsonia intracellularis in pig herds in different european countries","volume":"5","author":"Arnold","year":"2019","journal-title":"Porc. Health Manag."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1111\/j.1751-0813.2010.00558.x","article-title":"Prevalence of antibodies to Lawsonia Intracellularis in pig herds in Australia","volume":"88","author":"Holyoake","year":"2010","journal-title":"Aust. Vet. J."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Xiao, N., Li, J., Li, M., Zhou, H., Lin, H., and Fan, H. (2022). Isolation and in vitro cultivation of Lawsonia intracellularis from China. Vet. Microbiol., 270.","DOI":"10.1016\/j.vetmic.2022.109457"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.1016\/j.vaccine.2017.12.049","article-title":"A Novel inactivated vaccine against Lawsonia intracellularis induces rapid induction of humoral immunity, reduction of bacterial shedding and provides robust gut barrier function","volume":"36","author":"Roerink","year":"2018","journal-title":"Vaccine"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"105837","DOI":"10.1016\/j.prevetmed.2023.105837","article-title":"Effect of intramuscular vaccination against Lawsonia intracellularis on production parameters, diarrhea occurrence, antimicrobial treatment, bacterial shedding, and lean meat percentage in two danish naturally infected finisher pig herds","volume":"212","author":"Musse","year":"2023","journal-title":"Prev. Vet. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.vaccine.2014.10.084","article-title":"Vaccination of pigs with attenuated Lawsonia intracellularis induced acute phase protein responses and primed cell-mediated immunity without reduction in bacterial shedding after challenge","volume":"33","author":"Riber","year":"2015","journal-title":"Vaccine"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"559","DOI":"10.2460\/ajvr.2004.65.559","article-title":"evaluation of protective immunity in pigs following oral administration of an avirulent live vaccine of Lawsonia intracellularis","volume":"65","author":"Kroll","year":"2004","journal-title":"Am. J. Vet. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2149","DOI":"10.1016\/j.vaccine.2019.02.067","article-title":"Efficacy of a novel inactivated Lawsonia intracellularis vaccine in pigs against experimental infection and under field conditions","volume":"37","author":"Jacobs","year":"2019","journal-title":"Vaccine"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Daniel, A.G.S., Pereira, C.E.R., Dorella, F., Pereira, F.L., Laub, R.P., Andrade, M.R., Barrera-Zarate, J.A., Gabardo, M.P., Otoni, L.V.A., and Macedo, N.R. (2023). Synergic effect of Brachyspira hyodysenteriae and Lawsonia intracellularis coinfection: Anatomopathological and microbiome evaluation. Animals, 13.","DOI":"10.3390\/ani13162611"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1007\/s10344-010-0451-4","article-title":"Prevalence of Lawsonia intracellularis, Brachyspira hyodysenteriae, and Brachyspira pilosicoli infection in hunted wild boars (Sus scrofa) in Germany","volume":"57","author":"Reiner","year":"2011","journal-title":"Eur. J. Wildl. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"231","DOI":"10.4142\/jvs.2005.6.3.231","article-title":"Simultaneous detection of Lawsonia intracellularis, Brachyspira hyodysenteriae and Salmonella spp. in swine intestinal specimens by multiplex polymerase chain reaction","volume":"6","author":"Suh","year":"2005","journal-title":"J. Vet. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1136\/vr.122.23.554","article-title":"Serological diagnosis of the porcine proliferative enteropathies: Implications for aetiology and epidemiology","volume":"122","author":"Lawson","year":"1988","journal-title":"Vet. Rec."},{"key":"ref_15","first-page":"97","article-title":"Evidence of cell-mediated immune response and specific local mucosal immunoglobulin (Ig) A production against Lawsonia intracellularis in experimentally infected swine","volume":"74","author":"Guedes","year":"2010","journal-title":"Can. J. Vet. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1354\/vp.40-4-421","article-title":"Immunopathogenesis of experimentally induced proliferative enteropathy in pigs","volume":"40","author":"Macintyre","year":"2003","journal-title":"Vet. Pathol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/S0378-1135(02)00301-2","article-title":"Onset and duration of fecal shedding, cell-mediated and humoral immune responses in pigs after challenge with a pathogenic isolate or attenuated vaccine strain of Lawsonia intracellularis","volume":"91","author":"Guedes","year":"2003","journal-title":"Vet. Microbiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.vetmic.2013.02.004","article-title":"Immunological responses to vaccination following experimental Lawsonia intracellularis virulent challenge in pigs","volume":"164","author":"Nogueira","year":"2013","journal-title":"Vet. Microbiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/1297-9716-43-9","article-title":"Cell-mediated and humoral immune responses in pigs following primary and challenge-exposure to Lawsonia intracellularis","volume":"43","author":"Cordes","year":"2012","journal-title":"Vet. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"6737","DOI":"10.1128\/IAI.68.12.6737-6743.2000","article-title":"Gamma Interferon influences intestinal epithelial hyperplasia caused by Lawsonia intracellularis infection in mice","volume":"68","author":"Smith","year":"2000","journal-title":"Infect. Immun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/S0378-1135(03)00013-0","article-title":"Comparison of intestinal mucosa homogenate and pure culture of the homologous Lawsonia intracellularis isolate in reproducing proliferative enteropathy in swine","volume":"93","author":"Guedes","year":"2003","journal-title":"Vet. Microbiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/s13567-023-01180-y","article-title":"Improving the consistency of experimental swine dysentery inoculation strategies","volume":"54","author":"Nosach","year":"2023","journal-title":"Vet. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1006\/mcpr.1997.0129","article-title":"Specific detection of Serpulina hyodysenteriaeand potentially pathogenic weakly \u03b2-haemolytic porcine intestinal spirochetes by polymerase chain reaction targeting 23s rDNA","volume":"11","author":"Leser","year":"1997","journal-title":"Mol. Cell Probes"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5294","DOI":"10.2527\/jas.2012-6194","article-title":"Dietary plant extracts alleviate diarrhea and alter immune responses of weaned pigs experimentally infected with a pathogenic Escherichia coli","volume":"91","author":"Liu","year":"2013","journal-title":"J. Anim. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1177\/104063870301500506","article-title":"Preparation and characterization of polyclonal and monoclonal antibodies against Lawsonia intracellularis","volume":"15","author":"Guedes","year":"2003","journal-title":"J. Vet. Diagn. Investig."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"110461","DOI":"10.1016\/j.vetimm.2022.110461","article-title":"Rules of thumb to obtain, isolate, and preserve porcine peripheral blood mononuclear cells","volume":"251","year":"2022","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1136\/gut.35.11.1582","article-title":"Lymphoid and non-lymphoid cells in the epithelium and lamina propria of intestinal mucosa of pigs","volume":"35","author":"Rothkotter","year":"1994","journal-title":"Gut"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5150","DOI":"10.4049\/jimmunol.1101879","article-title":"Ileal Peyer\u2019s patches are not necessary for systemic B cell development and maintenance and do not contribute significantly to the overall B cell pool in swine","volume":"187","author":"Sinkora","year":"2011","journal-title":"J. Immunol."},{"key":"ref_29","unstructured":"Minist\u00e9rio da Agricultura Pecu\u00e1ria e Abastecimento (2009). Instru\u00e7\u00e3o Normativa N 26. de 9 de Julho de 2009, Minist\u00e9rio da Agricultura Pecu\u00e1ria e Abastecimento."},{"key":"#cr-split#-ref_30.1","unstructured":"The European Parliament, and The Council of the European Union (2019). Regulation"},{"key":"#cr-split#-ref_30.2","unstructured":"(EU) 2019\/6 of the European Parliament and of the Council of 11 December 2018. Off. J. Eur. Union, L4, 43-167."},{"key":"ref_31","unstructured":"The European Parliament, and The Council of the European Union (2001). Directive 2001\/82\/EC of the European Parliament and of the Council of 6 November 2001 on the Community Code Relating to Veterinary Medicinal Products. Off. J. Eur. Communities, L311, 1\u201366."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"110256","DOI":"10.1016\/j.vetimm.2021.110256","article-title":"Evaluation of immunogenicity and protection mediated by Lawsonia intracellularis subunit vaccines","volume":"237","author":"Fourie","year":"2021","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.vetmic.2011.06.003","article-title":"Microarray and cytokine analyses of field cases of pigs with diarrhoea","volume":"153","author":"Jacobson","year":"2011","journal-title":"Vet. Microbiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1186\/s13567-017-0465-y","article-title":"An avirulent Brachyspira hyodysenteriae strain elicits intestinal IgA and slows down spread of swine dysentery","volume":"48","author":"Mahu","year":"2017","journal-title":"Vet. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.vetimm.2011.05.035","article-title":"Current knowledge on porcine regulatory T cells","volume":"148","author":"Gerner","year":"2012","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Krishna, V.D., Kim, Y., Yang, M., Vannucci, F., Molitor, T., Torremorell, M., and Cheeran, M.C.-J. (2020). Immune responses to porcine epidemic diarrhea virus (PEDV) in swine and protection against subsequent infection. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0231723"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Pacheco, G.A., Andrade, C.A., G\u00e1lvez, N.M.S., V\u00e1zquez, Y., Rodr\u00edguez-Guilarte, L., Abarca, K., Gonz\u00e1lez, P.A., Bueno, S.M., and Kalergis, A.M. (2023). Characterization of the humoral and cellular immunity induced by a recombinant BCG vaccine for the respiratory syncytial virus in healthy adults. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1215893"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Pedrera, M., Soler, A., Sim\u00f3n, A., Casado, N., P\u00e9rez, C., Garc\u00eda-Casado, M.A., Fern\u00e1ndez-Pacheco, P., S\u00e1nchez-Cord\u00f3n, P.J., Arias, M., and Gallardo, C. (2024). Characterization of the protective cellular immune response in pigs immunized intradermally with the live attenuated african swine fever virus (ASFV) Lv17\/WB\/Rie1. Vaccines, 12.","DOI":"10.20944\/preprints202403.0438.v1"}],"container-title":["Animals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2615\/16\/1\/114\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T13:51:26Z","timestamp":1767189086000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2615\/16\/1\/114"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,31]]},"references-count":39,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["ani16010114"],"URL":"https:\/\/doi.org\/10.3390\/ani16010114","relation":{},"ISSN":["2076-2615"],"issn-type":[{"value":"2076-2615","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,31]]}}}