{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T16:56:16Z","timestamp":1790787376989,"version":"4.1.0"},"reference-count":60,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T00:00:00Z","timestamp":1736899200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T00:00:00Z","timestamp":1736899200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Vet Res"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Mycobacterium bovis<\/jats:italic>\n                      BCG is the human tuberculosis vaccine and is the oldest vaccine still in use today with over 4 billion people vaccinated since 1921. The BCG vaccine has also been investigated experimentally in cattle and wildlife by various routes including oral and parenteral. Thus far, oral vaccination studies of cattle have involved liquid BCG or liquid BCG incorporated into a lipid matrix. Lyophilization is an established technique used for stabilizing bioproducts such as vaccines.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In the current study, cattle were vaccinated in two phases. In each phase, cattle were divided into three groups. Group 1 received BCG injected SQ, Group 2 received liquid BCG delivered to the posterior oral cavity, Group 3 orally consumed lyophilized BCG contained within a gelatin capsule placed within a small amount of a commercial alfalfa product.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>No vaccinated cattle were positive by an interferon gamma release assay. All but 4 animals were negative by tuberculin skin testing prior to vaccination: the 4 non-negative animals being categorized as suspects. Sixteen weeks post-vaccination all but 1 animal was negative, it being categorized as a suspect. An in vitro antigen stimulation assay and flow cytometry were used to detect antigen-specific CD4, CD8 and \u03b3\u03b4 T cell responses following vaccination. Oral vaccination of animals with lyophilized BCG did not result in any increases in the frequency of CD4, CD8 or \u03b3\u03b4 T cell proliferative or IFN-\u03b3 responses at any of the time points analyzed in either phase 1 or 2. In contrast, vaccination with BCG SQ and liquid BCG delivered to the posterior pharynx, resulted in an increase in the frequency of proliferating and IFN-\u03b3-producing CD4 T cells with peak responses at 9\u201312\u00a0weeks post-vaccination. Similar to oral lyophilized BCG vaccinated animals, we did not observe any significant increases in the frequency of CD8 and \u03b3\u03b4 T cell proliferative and IFN-\u03b3 responses following SQ or oral liquid vaccinated animals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These data would suggest that vaccination with oral lyophilized BCG does not induce a measurable, antigen-specific cell mediated responses in the periphery, when compared to BCG administered SQ or liquid BCG administered via the oral route. However, vaccination with either SQ or liquid BCG delivered to the posterior pharynx does induce measurable CD4 T cell responses in the periphery.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12917-024-04452-7","type":"journal-article","created":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T00:57:51Z","timestamp":1736902671000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Immune responses of cattle vaccinated by various routes with Mycobacterium bovis Bacillus Calmette-Gu\u00e9rin (BCG)"],"prefix":"10.1186","volume":"21","author":[{"given":"Mitchell V.","family":"Palmer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soyoun","family":"Hwang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carly","family":"Kanipe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellie J.","family":"Putz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis Guilherme Virgilio","family":"Fernandes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Didkowska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola M.","family":"Boggiatto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,1,15]]},"reference":[{"key":"4452_CR1","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1007\/978-3-319-64371-7_8","volume":"1019","author":"AM Abdallah","year":"2017","unstructured":"Abdallah AM, Behr MA. Evolution and strain variation in BCG. Adv Exp Med Biol. 2017;1019:155\u201369.","journal-title":"Adv Exp Med Biol"},{"issue":"1","key":"4452_CR2","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1093\/clinids\/20.1.11","volume":"20","author":"PE Fine","year":"1995","unstructured":"Fine PE. Bacille Calmette-Guerin vaccines: a rough guide. Clin Infect Dis. 1995;20(1):11\u20134.","journal-title":"Clin Infect Dis"},{"issue":"8","key":"4452_CR3","doi-asserted-by":"publisher","first-page":"656","DOI":"10.1038\/nrmicro1211","volume":"3","author":"P Andersen","year":"2005","unstructured":"Andersen P, Doherty TM. The success and failure of BCG - implications for a novel tuberculosis vaccine. Nat Rev Microbiol. 2005;3(8):656\u201362.","journal-title":"Nat Rev Microbiol"},{"issue":"6","key":"4452_CR4","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1542\/peds.96.1.29","volume":"96","author":"GA Colditz","year":"1995","unstructured":"Colditz GA, Berkey CS, Mosteller F, Brewer TF, Wilson ME, Burdick E, Fineberg HV. The efficacy of bacillus Calmette-Guerin vaccination of newborns and infants in the prevention of tuberculosis: meta-analysis of the published literature. Pediatrics. 1995;96(6):29\u201335.","journal-title":"Pediatrics"},{"issue":"9517","key":"4452_CR5","doi-asserted-by":"publisher","first-page":"1173","DOI":"10.1016\/S0140-6736(06)68507-3","volume":"367","author":"BB Trunz","year":"2006","unstructured":"Trunz BB, Fine PEM, Dye C. Effect of BCG vaccination on childhood tuberculous meningitis and miliary tuberculosis worldwide: a meta-analysis and assessment of cost-effectiveness. The Lancet. 2006;367(9517):1173\u201380.","journal-title":"The Lancet"},{"issue":"16","key":"4452_CR6","doi-asserted-by":"publisher","first-page":"2611","DOI":"10.1016\/j.vaccine.2012.02.018","volume":"30","author":"WR Waters","year":"2012","unstructured":"Waters WR, Palmer MV, Buddle B, Vordermeier HM. Bovine tuberculosis vaccine research: Historical perspectives and recent advances. Vaccine. 2012;30(16):2611\u201322.","journal-title":"Vaccine"},{"issue":"27","key":"4452_CR7","doi-asserted-by":"publisher","first-page":"3581","DOI":"10.1016\/j.vaccine.2005.01.150","volume":"23","author":"BM Buddle","year":"2005","unstructured":"Buddle BM, Aldwell FE, Skinner MA, de Lisle GW, Denis M, Vordermeier HM, Hewinson RG, Wedlock DN. Effect of oral vaccination of cattle with lipid-formulated BCG on immune responses and protection against bovine tuberculosis. Vaccine. 2005;23(27):3581\u20139.","journal-title":"Vaccine"},{"issue":"6","key":"4452_CR8","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1016\/j.tube.2008.01.005","volume":"88","author":"BM Buddle","year":"2008","unstructured":"Buddle BM, Denis M, Aldwell FE, Martin Vordermeier H, Glyn Hewinson R, Neil Wedlock D. Vaccination of cattle with Mycobacterium bovis BCG by a combination of systemic and oral routes. Tuberculosis (Edinb). 2008;88(6):595\u2013600.","journal-title":"Tuberculosis (Edinb)"},{"issue":"1","key":"4452_CR9","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1128\/IAI.71.1.101-108.2003","volume":"71","author":"FE Aldwell","year":"2003","unstructured":"Aldwell FE, Tucker IG, de Lisle GW, Buddle BM. Oral delivery of Mycobacterium bovis BCG in a lipid formulation induces resistance to pulmonary tuberculosis in mice. Infect Immun. 2003;71(1):101\u20138.","journal-title":"Infect Immun"},{"issue":"1","key":"4452_CR10","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0168851","volume":"12","author":"E Gormley","year":"2017","unstructured":"Gormley E, Ni Bhuachalla D, O\u2019Keeffe J, Murphy D, Aldwell FE, Fitzsimons T, Stanley P, Tratalos JA, McGrath G, Fogarty N, et al. Oral vaccination of free-living badgers (Meles meles) with bacille Calmette Guerin (BCG) vaccine confers protection against tuberculosis. PLoS ONE. 2017;12(1): e0168851.","journal-title":"PLoS ONE"},{"issue":"2","key":"4452_CR11","doi-asserted-by":"publisher","first-page":"247","DOI":"10.7589\/0090-3558-44.2.247","volume":"44","author":"P Nol","year":"2008","unstructured":"Nol P, Palmer MV, Waters WR, Aldwell FE, Buddle BM, Triantis JM, Linke LM, Phillips GE, Thacker TC, Rhyan JC, et al. Efficacy of oral and parenteral routes of Mycobacterium bovis bacille Calmette-Guerin vaccination against experimental bovine tuberculosis in white-tailed deer (Odocoileus virginianus): a feasibility study. J Wildl Dis. 2008;44(2):247\u201359.","journal-title":"J Wildl Dis"},{"issue":"1","key":"4452_CR12","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/S0264-410X(03)00539-5","volume":"22","author":"FE Aldwell","year":"2003","unstructured":"Aldwell FE, Keen DL, Parlane NA, Skinner MA, de Lisle GW, Buddle BM. Oral vaccination with Mycobacterium bovis BCG in a lipid formulation induces resistance to pulmonary tuberculosis in brushtail possums. Vaccine. 2003;22(1):70\u20136.","journal-title":"Vaccine"},{"issue":"1","key":"4452_CR13","doi-asserted-by":"publisher","first-page":"119","DOI":"10.7589\/0090-3558-37.1.119","volume":"37","author":"CD MacInnes","year":"2001","unstructured":"MacInnes CD, Smith SM, Tinline RR, Ayers NR, Bachmann P, Ball DG, Calder LA, Crosgrey SJ, Fielding C, Hauschildt P, et al. Elimination of rabies from red foxes in eastern Ontario. J Wildl Dis. 2001;37(1):119\u201332.","journal-title":"J Wildl Dis"},{"issue":"2","key":"4452_CR14","doi-asserted-by":"publisher","first-page":"242","DOI":"10.7589\/0090-3558-43.2.242","volume":"43","author":"R Rosatte","year":"2007","unstructured":"Rosatte R, MacDonald E, Sobey K, Donovan D, Bruce L, Allan M, Silver A, Bennett K, Brown L, Macdonald K, et al. The elimination of raccoon rabies from Wolfe Island, Ontario: animal density and movements. J Wildl Dis. 2007;43(2):242\u201350.","journal-title":"J Wildl Dis"},{"issue":"3","key":"4452_CR15","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1007\/s10393-017-1273-6","volume":"14","author":"DJ Salkeld","year":"2017","unstructured":"Salkeld DJ. Vaccines for conservation: plague, prairie dogs & black-footed ferrets as a case study. EcoHealth. 2017;14(3):432\u20137.","journal-title":"EcoHealth"},{"key":"4452_CR16","volume-title":"Lyophilization of vaccines: Current trends","author":"GDJ Adams","year":"2003","unstructured":"Adams GDJ. Lyophilization of vaccines: Current trends. 2nd ed. Totowa, New Jersey: Humana Press; 2003.","edition":"2"},{"key":"4452_CR17","doi-asserted-by":"publisher","first-page":"1317","DOI":"10.1089\/107999099312993","volume":"19","author":"WL Trigona","year":"1999","unstructured":"Trigona WL, Hirano A, Brown WC, Estes DM. Immunoregulatory roles of interleukin-13 in cattle. J Interferon Cytokine Res. 1999;19:1317\u201324.","journal-title":"J Interferon Cytokine Res"},{"key":"4452_CR18","first-page":"85","volume":"11","author":"A Calmette","year":"1931","unstructured":"Calmette A. Preventive vaccination against tuberculosis with BCG. Proc Royal Soc Med. 1931;11:85\u201394.","journal-title":"Proc Royal Soc Med"},{"issue":"43","key":"4452_CR19","doi-asserted-by":"publisher","first-page":"6945","DOI":"10.1016\/j.vaccine.2010.07.086","volume":"28","author":"MM Ho","year":"2010","unstructured":"Ho MM, Southern J, Kang HN, Knezevic I. WHO Informal Consultation on standardization and evaluation of BCG vaccines Geneva, Switzerland 22\u201323 September 2009. Vaccine. 2010;28(43):6945\u201350.","journal-title":"Vaccine"},{"issue":"5","key":"4452_CR20","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1590\/S0074-02762005000500002","volume":"100","author":"TC Benevolo-de-Andrade","year":"2005","unstructured":"Benevolo-de-Andrade TC, Monteiro-Maia R, Cosgrove C, Castello-Branco LR. BCG Moreau Rio de Janeiro- an oral vaccine against tuberculosis. Mem Inst Oswaldo Cruz. 2005;100(5):459\u201365.","journal-title":"Mem Inst Oswaldo Cruz"},{"issue":"4","key":"4452_CR21","first-page":"377","volume":"1","author":"BM Buddle","year":"1997","unstructured":"Buddle BM, Aldwell FE, Keen DL, Parlane NA, Yates G, de Lisle GW. Intraduodenal vaccination of brushtail possums with bacille Calmette-Guerin enhances immune responses and protection against Mycobacterium bovis infection. Int J Tuberc Lung Dis. 1997;1(4):377\u201383.","journal-title":"Int J Tuberc Lung Dis"},{"key":"4452_CR22","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1016\/j.jconrel.2016.02.014","volume":"240","author":"AK Shakya","year":"2016","unstructured":"Shakya AK, Chowdhury MYE, Tao W, Gill HS. Mucosal vaccine delivery: Current state and a pediatric perspective. J Control Release. 2016;240:394\u2013413.","journal-title":"J Control Release"},{"issue":"1","key":"4452_CR23","doi-asserted-by":"publisher","first-page":"1264","DOI":"10.1038\/s41467-023-36907-0","volume":"14","author":"JG Mattathil","year":"2023","unstructured":"Mattathil JG, Volz A, Onabajo OO, Maynard S, Bixler SL, Shen XX, VargasInchaustegui D, Robert-Guroff M, Lebranche C, Tomaras G, et al. Direct intranodal tonsil vaccination with modified vaccinia Ankara vaccine protects macaques from highly pathogenic SIVmac251. Nat Commun. 2023;14(1):1264.","journal-title":"Nat Commun"},{"key":"4452_CR24","doi-asserted-by":"crossref","unstructured":"Nickel RA, Schummer E, Seiferle E: The viscera of domestic animals. In., 2 edn. Berlin: Verlag Paul Parley; 1979:52\u201356.","DOI":"10.1007\/978-1-4757-6814-5_2"},{"issue":"9","key":"4452_CR25","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1016\/S0167-5699(98)01307-3","volume":"19","author":"M Perry","year":"1998","unstructured":"Perry M, Whyte A. Immunology of the tonsils. Immunol Today. 1998;19(9):414\u201321.","journal-title":"Immunol Today"},{"key":"4452_CR26","unstructured":"Bernstein JM, Gorfien, J., Brandtzaeg, P.: The immunobiology of the tonsils and adenoid. In: Mucosal Immunology. edn. Edited by Orga P, L. San Diego: Academic Press. 1999:1339\u20131359."},{"key":"4452_CR27","doi-asserted-by":"crossref","unstructured":"Palmer MV, Stasko J, Waters WR, Thacker TC: Examination of the reticular epithelium of the bovine pharyngeal tonsil. Anat Rec. 2011(21809462).","DOI":"10.1002\/ar.21448"},{"issue":"3\u20134","key":"4452_CR28","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1016\/j.vetimm.2008.10.336","volume":"127","author":"MV Palmer","year":"2009","unstructured":"Palmer MV, Thacker TC, Waters WR. Histology, immunohistochemistry and ultrastructure of the bovine palatine tonsil with special emphasis on reticular epithelium. Vet Immunol Immunopathol. 2009;127(3\u20134):277\u201385.","journal-title":"Vet Immunol Immunopathol"},{"issue":"9","key":"4452_CR29","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1038\/nri1439","volume":"4","author":"H Kiyono","year":"2004","unstructured":"Kiyono H, Fukuyama S. NALT- versus Peyer\u2019s-patch-mediated mucosal immunity. Nat Rev Immunol. 2004;4(9):699\u2013710.","journal-title":"Nat Rev Immunol"},{"issue":"32","key":"4452_CR30","doi-asserted-by":"publisher","first-page":"3938","DOI":"10.1016\/j.vaccine.2017.06.022","volume":"35","author":"A Vos","year":"2017","unstructured":"Vos A, Freuling CM, Hundt B, Kaiser C, Nemitz S, Neubert A, Nolden T, Teifke JP, Te Kamp V, Ulrich R, et al. Oral vaccination of wildlife against rabies: Differences among host species in vaccine uptake efficiency. Vaccine. 2017;35(32):3938\u201344.","journal-title":"Vaccine"},{"issue":"1\u20132","key":"4452_CR31","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.vetmic.2009.09.044","volume":"142","author":"M Tignon","year":"2010","unstructured":"Tignon M, Kulcsar G, Haegeman A, Barna T, Fabian K, Levai R, Van der Stede Y, Farsang A, Vrancken R, Belak K, et al. Classical swine fever: comparison of oronasal immunisation with CP7E2alf marker and C-strain vaccines in domestic pigs. Vet Microbiol. 2010;142(1\u20132):59\u201368.","journal-title":"Vet Microbiol"},{"issue":"1\u20132","key":"4452_CR32","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.cellimm.2005.01.003","volume":"232","author":"M Denis","year":"2004","unstructured":"Denis M, Wedlock DN, Buddle BM. Ability of T cell subsets and their soluble mediators to modulate the replication of Mycobacterium bovis in bovine macrophages. Cell Immunol. 2004;232(1\u20132):1\u20138.","journal-title":"Cell Immunol"},{"issue":"6","key":"4452_CR33","doi-asserted-by":"publisher","first-page":"3026","DOI":"10.1128\/IAI.70.6.3026-3032.2002","volume":"70","author":"HM Vordermeier","year":"2002","unstructured":"Vordermeier HM, Chambers MA, Cockle PJ, Whelan AO, Simmons J, Hewinson RG. Correlation of ESAT-6-specific gamma interferon production with pathology in cattle following Mycobacterium bovis BCG vaccination against experimental bovine tuberculosis. Infect Immun. 2002;70(6):3026\u201332.","journal-title":"Infect Immun"},{"issue":"4","key":"4452_CR34","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1152\/advan.00066.2013","volume":"37","author":"ND Pennock","year":"2013","unstructured":"Pennock ND, White JT, Cross EW, Cheney EE, Tamburini BA, Kedl RM. T cell responses: naive to memory and everything in between. Adv Physiol Educ. 2013;37(4):273\u201383.","journal-title":"Adv Physiol Educ"},{"issue":"4","key":"4452_CR35","first-page":"15971601","volume":"66","author":"W Kunu","year":"2019","unstructured":"Kunu W, Jiwakanon J, Porntrakulpipat S. A bread-based lyophilized C-strain CSF virus vaccine as an oral vaccine in pigs. Transbound Emerg Dis. 2019;66(4):15971601.","journal-title":"Transbound Emerg Dis"},{"key":"4452_CR36","unstructured":"WHO: WHO guidance note: vaccine diluents. In. Geneva, Switzerland: World Health Organization. 2015:1\u201313."},{"issue":"12","key":"4452_CR37","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0008159","volume":"4","author":"V Abadie","year":"2009","unstructured":"Abadie V, Bonduelle O, Duffy D, Parizot C, Verrier B, Combadiere B. Original encounter with antigen determines antigen-presenting cell imprinting of the quality of the immune response in mice. PLoS ONE. 2009;4(12): e8159.","journal-title":"PLoS ONE"},{"issue":"7","key":"4452_CR38","doi-asserted-by":"publisher","first-page":"1023","DOI":"10.1084\/jem.20021348","volume":"198","author":"DW Mullins","year":"2003","unstructured":"Mullins DW, Sheasley SL, Ream RM, Bullock TN, Fu YX, Engelhard VH. Route of immunization with peptide-pulsed dendritic cells controls the distribution of memory and effector T cells in lymphoid tissues and determines the pattern of regional tumor control. J Exp Med. 2003;198(7):1023\u201334.","journal-title":"J Exp Med"},{"key":"4452_CR39","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.645210","volume":"12","author":"P Rosenbaum","year":"2021","unstructured":"Rosenbaum P, Tchitchek N, Joly C, Rodriguez Pozo A, Stimmer L, Langlois S, Hocini H, Gosse L, Pejoski D, Cosma A, et al. Vaccine Inoculation Route Modulates Early Immunity and Consequently Antigen-Specific Immune Response. Front Immunol. 2021;12: 645210.","journal-title":"Front Immunol"},{"issue":"7","key":"4452_CR40","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1016\/j.it.2005.05.003","volume":"26","author":"H Wiendl","year":"2005","unstructured":"Wiendl H, Hohlfeld R, Kieseier BC. Immunobiology of muscle: advances in understanding an immunological microenvironment. Trends Immunol. 2005;26(7):373\u201380.","journal-title":"Trends Immunol"},{"issue":"8","key":"4452_CR41","doi-asserted-by":"publisher","first-page":"811","DOI":"10.4161\/hv.7.8.16274","volume":"7","author":"B Combadiere","year":"2011","unstructured":"Combadiere B, Liard C. Transcutaneous and intradermal vaccination. Hum Vaccin. 2011;7(8):811\u201327.","journal-title":"Hum Vaccin"},{"key":"4452_CR42","doi-asserted-by":"publisher","first-page":"8303648","DOI":"10.1155\/2019\/8303648","volume":"2019","author":"E Criscuolo","year":"2019","unstructured":"Criscuolo E, Caputo V, Diotti RA, Sautto GA, Kirchenbaum GA, Clementi N. Alternative Methods of Vaccine Delivery: An Overview of Edible and Intradermal Vaccines. J Immunol Res. 2019;2019:8303648.","journal-title":"J Immunol Res"},{"issue":"2","key":"4452_CR43","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1111\/imm.13526","volume":"167","author":"VA Correa","year":"2022","unstructured":"Correa VA, Portilho AI, De Gaspari E. Vaccines, adjuvants and key factors for mucosal immune response. Immunology. 2022;167(2):124\u201338.","journal-title":"Immunology"},{"issue":"1","key":"4452_CR44","first-page":"1","volume":"10","author":"MN Martinez","year":"2022","unstructured":"Martinez MN, Papich MG, Fahmy R. Impact of gastrointestinal differences in veterinary species on the oral drug solubility, in vivo dissolution, and formulation of veterinary therapeutics. ADMET DMPK. 2022;10(1):1\u201325.","journal-title":"ADMET DMPK"},{"issue":"3","key":"4452_CR45","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1017\/S0021859600028732","volume":"94","author":"ET Clemens","year":"2009","unstructured":"Clemens ET, Stevens CE. A comparison of gastrointestinal transit time in ten species of mammal. J Agric Sci. 2009;94(3):735\u20137.","journal-title":"J Agric Sci"},{"key":"4452_CR46","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1016\/j.tube.2011.07.001","volume":"91","author":"B Buddle","year":"2011","unstructured":"Buddle B, Aldwell F, DeLisle G, Vordermeier H, Hewinson G, Wedlock DN. Low oral BCG doses fail to protect cattle against experimental challenge with Mycobacterium bovis. Tuberculosis. 2011;91:400\u20135.","journal-title":"Tuberculosis"},{"key":"4452_CR47","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1128\/CVI.00034-08","volume":"15","author":"DN Wedlock","year":"2008","unstructured":"Wedlock DN, Denis M, Painter GF, Ainge GD, Vordermeier HM, Hewinson RG, et al. Protection against bovine tuberculosis induced by BCG is enhanced by coadministration of adjuvanted mycobacterial protein vaccine, but abrogated by coadministration of adjuvant alone. Clin Vaccine Immunol. 2008;15:765\u201372.","journal-title":"Clin Vaccine Immunol"},{"issue":"1\u20132","key":"4452_CR48","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.vetimm.2007.04.005","volume":"118","author":"DN Wedlock","year":"2007","unstructured":"Wedlock DN, Denis M, Vordermeier HM, Hewinson RG, Buddle BM. Vaccination of cattle with Danish and Pasteur strains of Mycobacterium bovis BCG induce different levels of IFN gamma post-vaccination, but induce similar levels of protection against bovine tuberculosis. Vet Immunol Immunopathol. 2007;118(1\u20132):50\u20138.","journal-title":"Vet Immunol Immunopathol"},{"key":"4452_CR49","doi-asserted-by":"publisher","first-page":"S217","DOI":"10.1086\/313864","volume":"30","author":"DF Hoft","year":"2000","unstructured":"Hoft DF, Brown RM, Belshe RG. Mucosal bacilii Calmette-Guerin vaccination of humans inhibits delayed type hypersensitivity to purified protein derivative but induced mycobacteria-specific interferon gamma responses. Clin Infect Dis. 2000;30:S217\u2013222.","journal-title":"Clin Infect Dis"},{"key":"4452_CR50","doi-asserted-by":"publisher","first-page":"224","DOI":"10.12688\/f1000research.14085.1","volume":"7","author":"JB Dowd","year":"2018","unstructured":"Dowd JB, Fletcher HA, Boccia D. Social determinants and BCG efficacy: a call for a socio-biological approach to TB prevention. F1000Res. 2018;7:224.","journal-title":"F1000Res"},{"issue":"8986","key":"4452_CR51","doi-asserted-by":"publisher","first-page":"1339","DOI":"10.1016\/S0140-6736(95)92348-9","volume":"346","author":"PE Fine","year":"1995","unstructured":"Fine PE. Variation in protection by BCG: implications of and for heterologous immunity. Lancet. 1995;346(8986):1339\u201345.","journal-title":"Lancet"},{"issue":"10","key":"4452_CR52","doi-asserted-by":"publisher","first-page":"5603","DOI":"10.1172\/JCI133934","volume":"130","author":"LCJ de Bree","year":"2020","unstructured":"de Bree LCJ, Mourits VP, Koeken VA, Moorlag SJ, Janssen R, Folkman L, Barreca D, Krausgruber T, Fife-Gernedl V, Novakovic B, et al. Circadian rhythm influences induction of trained immunity by BCG vaccination. J Clin Invest. 2020;130(10):5603\u201317.","journal-title":"J Clin Invest"},{"issue":"24","key":"4452_CR53","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2024.07.010","volume":"42","author":"G Kilic","year":"2024","unstructured":"Kilic G, Debisarun PA, Alaswad A, Baltissen MP, Lamers LA, de Bree LCJ, Benn CS, Aaby P, Dijkstra H, Lemmers H, et al. Seasonal variation in BCG-induced trained immunity. Vaccine. 2024;42(24): 126109.","journal-title":"Vaccine"},{"issue":"4","key":"4452_CR54","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1038\/nrmicro3230","volume":"12","author":"C Nunes-Alves","year":"2014","unstructured":"Nunes-Alves C, Booty MG, Carpenter SM, Jayaraman P, Rothchild AC, Behar SM. In search of a new paradigm for protective immunity to TB. Nat Rev Microbiol. 2014;12(4):289\u201399.","journal-title":"Nat Rev Microbiol"},{"issue":"30","key":"4452_CR55","doi-asserted-by":"publisher","first-page":"12434","DOI":"10.1073\/pnas.0703510104","volume":"104","author":"H-W Mittr\u00fccker","year":"2007","unstructured":"Mittr\u00fccker H-W, Steinhoff U, K\u00f6hler AB, Krause M, Lazar D, Mex P, Miekley D, Kaufmann SHE. Poor correlation between BCG vaccination-induced T cell responses and protection against tuberculosis. Proc Natl Acad Sci. 2007;104(30):12434\u20139.","journal-title":"Proc Natl Acad Sci"},{"issue":"5","key":"4452_CR56","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0097031","volume":"9","author":"MV Palmer","year":"2014","unstructured":"Palmer MV, Thacker TC, Waters WR, Robbe-Austerman S. Oral vaccination of whitetailed deer (Odocoileus virginianus) with Mycobacterium bovis Bacillus Calmette-Gu\u00e9rin (BCG). PLoS ONE. 2014;9(5): e97031.","journal-title":"PLoS ONE"},{"key":"4452_CR57","volume-title":"Guide for the care and use of laboratory animals","author":"JC Garber","year":"2011","unstructured":"Garber JC. Guide for the care and use of laboratory animals. 8th ed. Washington, D.C.: The National Academies Press; 2011.","edition":"8"},{"key":"4452_CR58","unstructured":"FASS: Guide for the care and use of agricultural animals in research and teaching, Third edn. Champaign, IL: Federation of Animal Science Societies; 2010."},{"key":"4452_CR59","first-page":"11","volume":"2020","author":"PM Boggiatto","year":"1944","unstructured":"Boggiatto PM, Schaut RG, Olsen SC. Enhancing the detection of Brucella-specific CD4(+) T cell responses in cattle via in vitro antigenic expansion and restimulation. Front Immunol. 1944;2020:11.","journal-title":"Front Immunol"},{"issue":"4","key":"4452_CR60","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262","volume":"25","author":"KJ Livak","year":"2001","unstructured":"Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25(4): 402408.","journal-title":"Methods"}],"container-title":["BMC Veterinary Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12917-024-04452-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12917-024-04452-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12917-024-04452-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T01:47:02Z","timestamp":1736905622000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcvetres.biomedcentral.com\/articles\/10.1186\/s12917-024-04452-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,15]]},"references-count":60,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["4452"],"URL":"https:\/\/doi.org\/10.1186\/s12917-024-04452-7","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-5227374\/v1","asserted-by":"object"}]},"ISSN":["1746-6148"],"issn-type":[{"value":"1746-6148","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,15]]},"assertion":[{"value":"8 October 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 December 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 January 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Cattle were purchased from a private owner and became the property of USDA. All experimental animal procedures were conducted in accordance with recommendations in the Care and Use of Laboratory Animals of the National Institutes of Health and the Guide for the Care and Use of Agricultural Animals in Research and Teaching [57, 58]. Animal related procedures were also approved the USDA National Animal Disease Center Animal Care and Use Committee (protocol #ARS-2021\u2013952).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"19"}}