{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T19:29:59Z","timestamp":1789586999617,"version":"build-2803163510"},"reference-count":47,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T00:00:00Z","timestamp":1711929600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012190","name":"Results Driven Agriculture Research","doi-asserted-by":"publisher","award":["2023F281R"],"award-info":[{"award-number":["2023F281R"]}],"id":[{"id":"10.13039\/100012190","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Alberta Beef Producers","award":["2023F281R"],"award-info":[{"award-number":["2023F281R"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background: Mannheimia haemolytica is a bovine respiratory pathogen commonly associated with bacterial bronchopneumonia. Current vaccine strategies have shown variable efficacy in feedlot cattle, and therefore novel vaccines are needed. Bacillus subtilis spores have been investigated as a mucosal vaccine platform, due to their ability to bind and present antigens to the mucosa and act as an adjuvant. The aim of this study was to develop two spore-based mucosal vaccines targeting M. haemolytica and evaluate their immunogenicity in mice. Methods: Two antigen constructs composed of cholera toxin B subunit, M. haemolytica leukotoxin, and either the M. haemolytica outer membrane protein PlpE (MhCP1) or GS60 (MhCP2) were synthesized, purified and then bound to spores as vaccines. In two separate mice trials, the spore-bound vaccines (Spore-MhCP1 and Spore-MhCP2) were administered to mice through intranasal and intragastric routes, while free antigens were administered intranasally and intramuscularly. Unbound spores were also evaluated intranasally. Antigen-specific serum IgG and mucosal IgA from bronchoalveolar lavage, feces, and saliva were measured after vaccination. Mice sera from all treatment groups were assessed for their bactericidal activity against M. haemolytica. Results: In both mice experiments, intramuscular immunization induced the strongest serum IgG antibody response. However, the intranasal administration of Spore-MhCP1 and Spore-MhCP2 elicited the greatest secretory IgA-specific response against leukotoxin, PlpE, and GS60 in bronchoalveolar lavage, saliva, and feces (p &lt; 0.05). Compared to the intranasal administration of free antigen, spore-bound antigen groups showed greater bactericidal activity against M. haemolytica (p &lt; 0.05). Conclusions: Since intranasally delivered Spore-MhCP1 and Spore-MhCP2 elicited both systemic and mucosal immune responses in mice, these vaccines may have potential to mitigate lung infection in cattle by restricting M. haemolytica colonization and proliferation in the respiratory tract. The efficacy of these mucosal spore-based vaccines merits further assessment against M. haemolytica in cattle.<\/jats:p>","DOI":"10.3390\/vaccines12040375","type":"journal-article","created":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T05:44:36Z","timestamp":1711950276000},"page":"375","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Mucosal Immunization with Spore-Based Vaccines against Mannheimia haemolytica Enhances Antigen-Specific Immunity"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3582-2915","authenticated-orcid":false,"given":"Muhammed Salah","family":"Uddin","sequence":"first","affiliation":[{"name":"Lethbridge Research and Development Centre, Agriculture and Agri-Food Canada, Lethbridge, AB T1J 4B1, Canada"},{"name":"Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB T6G 2P5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"Kaldis","sequence":"additional","affiliation":[{"name":"London Research and Development Centre, Agriculture and Agri-Food Canada, London, ON N5V 4T3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rima","family":"Menassa","sequence":"additional","affiliation":[{"name":"London Research and Development Centre, Agriculture and Agri-Food Canada, London, ON N5V 4T3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Ortiz Guluarte","sequence":"additional","affiliation":[{"name":"Lethbridge Research and Development Centre, Agriculture and Agri-Food Canada, Lethbridge, AB T1J 4B1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel R.","family":"Barreda","sequence":"additional","affiliation":[{"name":"Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB T6G 2P5, Canada"},{"name":"Department of Biological Sciences, University of Alberta, Edmonton, AB T6G 2R3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le Luo","family":"Guan","sequence":"additional","affiliation":[{"name":"Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB T6G 2P5, Canada"},{"name":"Faculty of Land and Food Systems, University of British Columbia, Vancouver, BC V6T 1Z4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trevor W.","family":"Alexander","sequence":"additional","affiliation":[{"name":"Lethbridge Research and Development Centre, Agriculture and Agri-Food Canada, Lethbridge, AB T1J 4B1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Alexander, T.W., Cook, S., Klima, C.L., Topp, E., and McAllister, T.A. 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