{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T19:49:44Z","timestamp":1770839384475,"version":"3.50.1"},"reference-count":13,"publisher":"American Society for Microbiology","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin. Vaccine Immunol."],"published-print":{"date-parts":[[2011,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Blastomycosis is a severe, commonly fatal infection caused by the dimorphic fungus<jats:named-content content-type=\"genus-species\">Blastomyces dermatitidis<\/jats:named-content>in dogs that live in the United States, Canada, and parts of Africa. The cost of treating an infection can be expensive, and no vaccine against this infection is commercially available. A genetically engineered live-attenuated strain of<jats:named-content content-type=\"genus-species\">B. dermatitidis<\/jats:named-content>lacking the major virulence factor BAD-1 successfully vaccinates against lethal experimental infection in mice. Here we studied the safety, toxicity, and immunogenicity of this strain as a vaccine in dogs, using 25 beagles at a teaching laboratory and 78 foxhounds in a field trial. In the beagles, escalating doses of live vaccine ranging from 2 \u00d7 10<jats:sup>4<\/jats:sup>to 2 \u00d7 10<jats:sup>7<\/jats:sup>yeast cells given subcutaneously were safe and did not disseminate to the lung or induce systemic illness, but a dose of &lt;2 \u00d7 10<jats:sup>6<\/jats:sup>yeast cells induced less fever and local inflammation. A vaccine dose of 10<jats:sup>5<\/jats:sup>yeast cells was also well tolerated in vaccinated foxhounds who had never had blastomycosis; however, vaccinated dogs with prior infection had more local reactions at the vaccine site. The draining lymph node cells and peripheral blood lymphocytes from vaccinated dogs demonstrated gamma interferon (IFN-\u03b3), tumor necrosis factor alpha (TNF-\u03b1), and granulocyte-macrophage colony-stimulating factor (GM-CSF) specifically in response to stimulation with<jats:named-content content-type=\"genus-species\">Blastomyces<\/jats:named-content>antigens. Thus, the live-attenuated vaccine against blastomycosis studied here proved safe, well tolerated, and immunogenic in dogs and merits further studies of vaccine efficacy.<\/jats:p>","DOI":"10.1128\/cvi.00560-10","type":"journal-article","created":{"date-parts":[[2011,3,3]],"date-time":"2011-03-03T03:26:21Z","timestamp":1299122781000},"page":"783-789","source":"Crossref","is-referenced-by-count":24,"title":["Safety, Tolerability, and Immunogenicity of a Recombinant, Genetically Engineered, Live-Attenuated Vaccine against Canine Blastomycosis"],"prefix":"10.1128","volume":"18","author":[{"given":"Marcel","family":"W\u00fcthrich","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Theerapong","family":"Krajaejun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valerie","family":"Shearn-Bochsler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chris","family":"Bass","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanna I.","family":"Filutowicz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alfred M.","family":"Legendre","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruce S.","family":"Klein","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","published-online":{"date-parts":[[2011,3,2]]},"reference":[{"key":"key20180919073512_B1","doi-asserted-by":"crossref","first-page":"7389","DOI":"10.4049\/jimmunol.162.12.7389","article-title":"Complex requirements for nascent and memory immunity in pulmonary histoplasmosis","volume":"162","author":"Allendorfer","year":"1999","journal-title":"J. Immunol."},{"key":"key20180919073512_B2","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1080\/02681219580000361","article-title":"The epidemiology of blastomycosis in dogs: north central Wisconsin, U. S. A.","volume":"33","author":"Baumgardner","year":"1995","journal-title":"J. Med. Vet. Mycol."},{"key":"key20180919073512_B3","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1084\/jem.189.8.1207","article-title":"Targeted gene disruption reveals an adhesin indispensable for pathogenicity of Blastomyces dermatitidis","volume":"189","author":"Brandhorst","year":"1999","journal-title":"J. Exp. Med."},{"key":"key20180919073512_B4","first-page":"611","volume-title":"Biostatistics: a methodology for the health sciences","author":"Fisher","year":"1993"},{"key":"key20180919073512_B5","first-page":"695","article-title":"Mouse model of pulmonary blastomycosis: utility, simplicity, and quantitative parameters","volume":"117","author":"Harvey","year":"1978","journal-title":"Am. Rev. Respir. Dis."},{"key":"key20180919073512_B6","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1006\/abio.1999.4461","article-title":"Quantitation of dihydropyrimidine dehydrogenase expression by real-time reverse transcription polymerase chain reaction","volume":"278","author":"Johnson","year":"2000","journal-title":"Anal. Biochem."},{"key":"key20180919073512_B7","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1172\/JCI114406","article-title":"Isolation, purification, and radiolabeling of a novel 120-kD surface protein on Blastomyces dermatitidis yeasts to detect antibody in infected patients","volume":"85","author":"Klein","year":"1990","journal-title":"J. Clin. Invest."},{"key":"key20180919073512_B8","doi-asserted-by":"crossref","first-page":"554","DOI":"10.2460\/ajvr.2000.61.554","article-title":"Canine antibody response to Blastomyces dermatitidis WI-1 antigen","volume":"61","author":"Klein","year":"2000","journal-title":"Am. J. Vet. Res."},{"key":"key20180919073512_B9","volume-title":"Blastomycosis","author":"Legendre","year":"2006"},{"key":"key20180919073512_B10","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1172\/JCI11037","article-title":"Mutation of the WI-1 gene yields an attenuated Blastomyces dermatitidis strain that induces host resistance","volume":"106","author":"W\u00fcthrich","year":"2000","journal-title":"J. Clin. Invest."},{"key":"key20180919073512_B11","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1084\/jem.20030109","article-title":"Vaccine immunity to pathogenic fungi overcomes the requirement for CD4 help in exogenous antigen presentation to CD8+ T cells: implications for vaccine development in immune-deficient hosts","volume":"197","author":"W\u00fcthrich","year":"2003","journal-title":"J. Exp. Med."},{"key":"key20180919073512_B12","doi-asserted-by":"crossref","first-page":"6969","DOI":"10.4049\/jimmunol.169.12.6969","article-title":"Requisite elements in vaccine immunity to Blastomyces dermatitidis: plasticity uncovers vaccine potential in immune-deficient hosts","volume":"169","author":"W\u00fcthrich","year":"2002","journal-title":"J. Immunol."},{"key":"key20180919073512_B13","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1172\/JCI43984","article-title":"Vaccine-induced protection against 3 systemic mycoses endemic to North America requires Th17 cells in mice","volume":"121","author":"W\u00fcthrich","year":"2011","journal-title":"J. Clin. Invest."}],"container-title":["Clinical and Vaccine Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1128\/CVI.00560-10","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,5]],"date-time":"2023-06-05T13:26:21Z","timestamp":1685971581000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/CVI.00560-10"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,3,2]]},"references-count":13,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2011,5,3]]},"published-print":{"date-parts":[[2011,5]]}},"alternative-id":["10.1128\/CVI.00560-10"],"URL":"https:\/\/doi.org\/10.1128\/cvi.00560-10","relation":{},"ISSN":["1556-6811","1556-679X"],"issn-type":[{"value":"1556-6811","type":"print"},{"value":"1556-679X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,3,2]]}}}