{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T15:21:49Z","timestamp":1787757709621,"version":"build-2784847793"},"reference-count":16,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>\n                      The fusion protein H65, composed of\n                      <jats:italic toggle=\"yes\">Mycobacterium tuberculosis<\/jats:italic>\n                      (TB) ESX-secreted antigens, has improved the bacillus Calmette\u2013Guerin-induced immune protection in a mouse model of bovine TB when formulated in the liposomal adjuvant CAF01. In this study, we aimed to evaluate the protective efficacy of an attenuated\n                      <jats:italic toggle=\"yes\">Mycobacterium bovis<\/jats:italic>\n                      strain \u2013 a mutant in\n                      <jats:italic toggle=\"yes\">mce2<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">phoP<\/jats:italic>\n                      genes \u2013 combined with H65+CAF01 immunization. We evaluated the protection of Mb\u0394\n                      <jats:italic toggle=\"yes\">mce2-phoP<\/jats:italic>\n                      alone or combined with H65+CAF01 against\n                      <jats:italic toggle=\"yes\">M. bovis<\/jats:italic>\n                      challenge in mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      Groups of BALBc mice were inoculated with the vaccine candidates or phosphate buffered saline (PBS), and 6 weeks after the last immunization, the animals were aerogenically challenged with virulent\n                      <jats:italic toggle=\"yes\">M. bovis<\/jats:italic>\n                      . Bacterial load in organs was counted after 45 days of the challenge. One-way analysis of variance and Bonferroni's posttest were used for statistical analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>All vaccinated mice showed reduced bacterial loads in lungs compared to unvaccinated animals. However, the protection level was similar between vaccinated groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>\n                      The Mb\u0394\n                      <jats:italic toggle=\"yes\">mce2-phoP<\/jats:italic>\n                      strain combined with three doses of H65+CAF01 induced equivalent protection than the Mb\u0394\n                      <jats:italic toggle=\"yes\">mce2-phoP<\/jats:italic>\n                      strain alone. Thus, the use of combined vaccination strategies requires a careful analysis of the potential interactions of each of their components with the host's immune system.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.4103\/ijmy.ijmy_201_21","type":"journal-article","created":{"date-parts":[[2021,12,12]],"date-time":"2021-12-12T15:14:06Z","timestamp":1639322046000},"page":"411-413","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":5,"title":["H65 Fusion Protein Fails to Improve the Protection of a Rationally Attenuated Live Vaccine Candidate against Bovine Tuberculosis in a Mouse Model of Tuberculosis"],"prefix":"10.4103","volume":"10","author":[{"given":"Elizabeth A.","family":"Garc\u00eda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico C.","family":"Blanco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiana","family":"Bigi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-10-20240902","first-page":"229","article-title":"The genomics of mycobacteria","volume":"35","author":"Viale","year":"2016","journal-title":"Rev Sci Tech"},{"key":"R2-10-20240902","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1093\/epirev\/mxz002","article-title":"Zoonotic tuberculosis in humans: Control, surveillance, and the one health approach","volume":"41","author":"Macedo Couto","year":"2019","journal-title":"Epidemiol Rev"},{"key":"R3-10-20240902","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.vetmic.2011.02.021","article-title":"Update on vaccination of cattle and wildlife populations against 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Sci"},{"key":"R10-10-20240902","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.vetmic.2018.06.016","article-title":"Characterization of the two component regulatory system PhoPR in Mycobacterium bovis","volume":"222","author":"Garc\u00eda","year":"2018","journal-title":"Vet Microbiol"},{"key":"R11-10-20240902","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1073\/pnas.1314973111","article-title":"Tuberculosis vaccine with high predicted population coverage and compatibility with modern diagnostics","volume":"111","author":"Knudsen","year":"2014","journal-title":"Proc Natl Acad Sci U S A"},{"key":"R12-10-20240902","doi-asserted-by":"crossref","first-page":"1707","DOI":"10.1016\/j.bbamcr.2013.11.003","article-title":"Take five \u2013 Type VII secretion systems of mycobacteria","volume":"1843","author":"Houben","year":"2014","journal-title":"Biochim Biophys Acta"},{"key":"R13-10-20240902","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.tube.2011.11.005","article-title":"The ins and outs of Mycobacterium tuberculosis protein export","volume":"92","author":"Ligon","year":"2012","journal-title":"Tuberculosis (Edinb"},{"key":"R14-10-20240902","doi-asserted-by":"crossref","first-page":"e1002621","DOI":"10.1371\/journal.ppat.1002621","article-title":"Virulence regulator EspR of Mycobacterium tuberculosis is a nucleoid-associated protein","volume":"8","author":"Blasco","year":"2012","journal-title":"PLoS Pathog"},{"key":"R15-10-20240902","doi-asserted-by":"crossref","first-page":"19018","DOI":"10.1074\/jbc.M116.746289","article-title":"EspR-dependent ESAT-6 protein secretion of Mycobacterium tuberculosis requires the presence of virulence regulator PhoP","volume":"291","author":"Anil Kumar","year":"2016","journal-title":"J Biol 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