{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:43:04Z","timestamp":1787319784925,"version":"build-2736575974"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,4,4]],"date-time":"2024-04-04T00:00:00Z","timestamp":1712188800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Bovine respiratory disease (BRD) is one of the most common diseases in the cattle industry worldwide; it is caused by multiple bacterial or viral coinfections, of which\n                    <jats:italic>Mycoplasma bovis<\/jats:italic>\n                    (\n                    <jats:italic>M. bovis<\/jats:italic>\n                    ) and bovine herpesvirus type 1 (BoHV-1) are the most notable pathogens. Although live vaccines have demonstrated better efficacy against BRD induced by both pathogens, there are no combined live and marker vaccines. Therefore, we developed an attenuated and marker\n                    <jats:italic>M. bovis<\/jats:italic>\n                    -BoHV-1 combined vaccine based on the\n                    <jats:italic>M. bovis<\/jats:italic>\n                    HB150 and BoHV-1 gG-\/tk- strain previously constructed in our lab and evaluated in rabbits. This study aimed to further evaluate its safety and protective efficacy in cattle using different antigen ratios. After immunization, all vaccinated cattle had a normal rectal temperature and mental status without respiratory symptoms. CD4\n                    <jats:sup>+<\/jats:sup>\n                    , CD8\n                    <jats:sup>+<\/jats:sup>\n                    , and CD19\n                    <jats:sup>+<\/jats:sup>\n                    cells significantly increased in immunized cattle and induced higher humoral and cellular immune responses, and the expression of key cytokines such as IL-4, IL-12, TNF-\u03b1, and IFN-\u03b3 can be promoted after vaccination. The 1.0\u00a0\u00d7 10\n                    <jats:sup>8<\/jats:sup>\n                    CFU of\n                    <jats:italic>M. bovis<\/jats:italic>\n                    HB150 and 1.0 \u00d7 10\n                    <jats:sup>6<\/jats:sup>\n                    TCID\n                    <jats:sub>50<\/jats:sub>\n                    BoHV-1 gG-\/tk- combined strain elicited the most antibodies while significantly increasing IgG and cellular immunity after challenge. In conclusion, the\n                    <jats:italic>M. bovis<\/jats:italic>\n                    HB150 and BoHV-1 gG-\/tk- combined strain was clinically safe and protective in calves; the mix of 1.0 \u00d7 10\n                    <jats:sup>8<\/jats:sup>\n                    CFU of\n                    <jats:italic>M. bovis<\/jats:italic>\n                    HB150 and 1.0 \u00d7 10\n                    <jats:sup>6<\/jats:sup>\n                    TCID\n                    <jats:sub>50<\/jats:sub>\n                    BoHV-1 gG-\/tk- strain was most promising due to its low amount of shedding and highest humoral and cellular immune responses compared with others. This study introduces an\n                    <jats:italic>M. bovis<\/jats:italic>\n                    -BoHV-1 combined vaccine for application in the cattle industry.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2024.1367253","type":"journal-article","created":{"date-parts":[[2024,4,4]],"date-time":"2024-04-04T01:01:49Z","timestamp":1712192509000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Investigation of the safety and protective efficacy of an attenuated and marker M. bovis-BoHV-1 combined vaccine in bovines"],"prefix":"10.3389","volume":"15","author":[{"given":"Sen","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoxing","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yisheng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowen","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhao","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhijie","family":"Xiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenying","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianguo","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aizhen","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingyu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,4,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1186\/s40168-017-0372-5","article-title":"Characterization of the upper and lower respiratory tract microbiota in Piedmontese calves","volume":"5","author":"Nicola","year":"2017","journal-title":"Microbiome"},{"key":"B2","article-title":"Risk factors for initial respiratory disease in United States' feedlots based on producer-collected daily morbidity counts","volume":"49","author":"Sanderson","year":"2008","journal-title":"Can Vet J-Veterinaire Canadienne"},{"key":"B3","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1016\/j.cvfa.2020.03.008","article-title":"The effect of market forces on bovine respiratory disease","volume":"36","author":"Peel","year":"2020","journal-title":"Vet Clin N Am-Food A"},{"key":"B4","doi-asserted-by":"publisher","first-page":"994","DOI":"10.3390\/pathogens9120994","article-title":"Infections: occurrence, pathogenesis, diagnosis and control, including prevention and therapy","volume":"9","author":"Dudek","year":"2020","journal-title":"Pathogens"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.2c00618","article-title":"Bovine airway models: approaches for investigating bovine respiratory disease","volume":"9","author":"Gandhi","year":"2023","journal-title":"ACS Infect Dis"},{"key":"B6","doi-asserted-by":"publisher","first-page":"skaa005","DOI":"10.1093\/jas\/skaa005","article-title":"An evaluation of the economic effects of bovine respiratory disease on animal performance, carcass traits, and economic outcomes in feedlot cattle defined using four BRD diagnosis methods","volume":"98","author":"Blakebrough-Hall","year":"2020","journal-title":"J\u00a0Anim Sci"},{"key":"B7","article-title":"The epidemiology of bovine respiratory disease: What is the evidence for preventive measures","volume":"51","author":"Taylor","year":"2010","journal-title":"Can Vet J-Revue Veterinaire Can"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.02485-13","article-title":"Pathogens of bovine respiratory disease in north american feedlots conferring multidrug resistance via integrative conjugative elements","volume":"52","author":"Klima","year":"2014","journal-title":"J Clin Microbiol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0038239","article-title":"Comparative geno-plasticity analysis of HB0801 (Chinese isolate)","volume":"7","author":"Qi","year":"2012","journal-title":"PloS One"},{"key":"B10","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.actatropica.2018.07.024","article-title":"Meta-analysis of prevalence of bovine herpes virus 1 in cattle in Mainland China","volume":"187","author":"Chen","year":"2018","journal-title":"Acta Trop"},{"key":"B11","doi-asserted-by":"publisher","first-page":"104594","DOI":"10.1016\/j.micpath.2020.104594","article-title":"Investigation of viral pathogens in cattle with bovine respiratory disease complex in Inner Mongolia, China","volume":"153","author":"Guo","year":"2021","journal-title":"Microb Pathog"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2013.12.004","article-title":"Attenuated strains provide protection against virulent infection in calves","volume":"32","author":"Zhang","year":"2014","journal-title":"Vaccine"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2011.09.050","article-title":"Attenuation of bovine herpesvirus type 1 by deletion of its glycoprotein G and genes and protection against virulent viral challenge","volume":"29","author":"Zhang","year":"2011","journal-title":"Vaccine"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1698","DOI":"10.3390\/vaccines11111698","article-title":"The safety and protective efficacy evaluation of an attenuated-boHV-1 bivalent vaccine in rabbits","volume":"11","author":"Zhang","year":"2023","journal-title":"Vaccines-Basel"},{"key":"B15","doi-asserted-by":"publisher","first-page":"656","DOI":"10.3390\/genes10090656","article-title":"Calves infected with virulent and attenuated strains have upregulated Th17 inflammatory and Th1 protective responses, respectively","volume":"10","author":"Chao","year":"2019","journal-title":"Genes-Basel"},{"key":"B16","doi-asserted-by":"publisher","first-page":"253","DOI":"10.3390\/vetsci8110253","article-title":"Characterization of boHV-1 gG-\/tk-\/gE- mutant in differential protein expression, virulence, and immunity","volume":"8","author":"Marawan","year":"2021","journal-title":"Veterinary Sci"},{"key":"B17","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/j.cvfa.2010.03.001","article-title":"Innate immunology of bovine respiratory disease","volume":"26","author":"Ackermann","year":"2010","journal-title":"Vet Clin N Am-Food A"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2019.04.005","article-title":"Contribution of the mucosal microbiota to bovine respiratory health","volume":"27","author":"Zeineldin","year":"2019","journal-title":"Trends Microbiol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0179215","article-title":"Weaned beef calves fed selenium-biofortified alfalfa hay have an enriched nasal microbiota compared with healthy controls","volume":"12","author":"Hall","year":"2017","journal-title":"PloS One"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.rvsc.2020.11.002","article-title":"Bovine respiratory disease in beef calves supported long transport stress: An epidemiological study and strategies for control and prevention","volume":"135","author":"Pratelli","year":"2021","journal-title":"Res Vet Sci"},{"key":"B21","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1186\/s12866-017-1042-2","article-title":"Relationship between nasopharyngeal and bronchoalveolar microbial communities in clinically healthy feedlot cattle","volume":"17","author":"Zeineldin","year":"2017","journal-title":"BMC Microbiol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2017.03.095","article-title":"Status of the development of a vaccine against","volume":"35","author":"Perez-Casal","year":"2017","journal-title":"Vaccine"},{"key":"B23","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1128\/CMR.00010-16","article-title":"Respiratory syncytial virus: infection, detection, and new options for prevention and treatment","volume":"30","author":"Griffiths","year":"2017","journal-title":"Clin Microbiol Rev"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1556\/avet.56.2008.4.6","article-title":"Field efficacy of combination vaccines against bovine respiratory pathogens in calves","volume":"56","author":"Makoschey","year":"2008","journal-title":"Acta Vet Hung"},{"key":"B25","article-title":"A comparison of 2 vaccination programs in feedlot calves at ultra-high risk of developing undifferentiated fever\/bovine respiratory disease","volume":"49","author":"Wildman","year":"2008","journal-title":"Can Veterinary Journal-Revue Veterinaire Canadienne"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/S0264-410X(99)00324-2","article-title":"The efficacy of modified-live bovine respiratory syncytial virus vaccines in experimentally infected calves","volume":"18","author":"West","year":"1999","journal-title":"Vaccine"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.2460\/javma.235.5.580","article-title":"Comparison of single vaccination versus revaccination with a modified-live virus vaccine containing bovine herpesvirus-1, bovine viral diarrhea virus (types 1a and 2a), parainfluenza type 3 virus, and bovine respiratory syncytial virus in the prevention of bovine respiratory disease in cattle","volume":"235","author":"Step","year":"2009","journal-title":"Javma-J Am Vet Med A"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1017\/S1466252313000054","article-title":"Immunity to bovine herpesvirus 1: II. Adaptive immunity and vaccinology","volume":"14","author":"Levings","year":"2013","journal-title":"Anim Health Res Rev"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1586\/14760584.6.3.369","article-title":"Cell-mediated immune responses induced by BHV-1: rational vaccine design","volume":"6","author":"Littel-van den Hurk","year":"2007","journal-title":"Expert Rev Vaccines"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.tvjl.2014.05.040","article-title":"Epidemiology and control of bovine herpesvirus 1 infection in Europe","volume":"201","author":"Raaperi","year":"2014","journal-title":"Veterinary J"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1007\/978-94-024-0921-5_6","article-title":"Regulation of interleukin-12 production in antigen-presenting cells","volume":"941","author":"Zheng","year":"2016","journal-title":"Adv Exp Med Biol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetimm.2011.07.022","article-title":"Response of proinflammatory and anti-inflammatory cytokines in calves with subclinical bovine viral diarrhea challenged with bovine herpesvirus-1","volume":"144","author":"Risalde","year":"2011","journal-title":"Vet Immunol Immunop"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1002\/(ISSN)1521-4141","article-title":"Historical insights into cytokines","volume":"37","author":"Dinarello","year":"2007","journal-title":"Eur J Immunol"},{"key":"B34","doi-asserted-by":"publisher","first-page":"346","DOI":"10.3390\/v10070346","article-title":"Display of porcine epidemic diarrhea virus spike protein on baculovirus to improve immunogenicity and protective efficacy","volume":"10","author":"Chang","year":"2018","journal-title":"Viruses-Basel"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/S0042-6822(95)80057-3","article-title":"The role of the major tegument protein vp8 of bovine herpesvirus-1 in infection and immunity","volume":"206","author":"Littelvandenhurk","year":"1995","journal-title":"Virology"},{"key":"B36","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/s0165-2427(03)00056-4","article-title":"Characterization of the immune response to lung infection","volume":"94","author":"Bush","year":"2003","journal-title":"Vet Immunol Immunop"},{"key":"B37","doi-asserted-by":"publisher","first-page":"549","DOI":"10.3390\/vaccines9060549","article-title":"Recent developments in vaccines for bovine mycoplasmoses caused by and subsp","volume":"9","author":"Dudek","year":"2021","journal-title":"Vaccines-Basel"},{"key":"B38","doi-asserted-by":"publisher","first-page":"785","DOI":"10.3390\/vaccines11040785","article-title":"The cell-mediated immune response against (BoHV-1) infection and vaccination","volume":"11","author":"Righi","year":"2023","journal-title":"Vaccines-Basel"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1367253\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,4]],"date-time":"2024-04-04T01:01:51Z","timestamp":1712192511000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1367253\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,4]]},"references-count":38,"alternative-id":["10.3389\/fimmu.2024.1367253"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2024.1367253","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,4]]},"article-number":"1367253"}}