{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T09:00:49Z","timestamp":1790413249535,"version":"4.1.0"},"reference-count":18,"publisher":"American Veterinary Medical Association (AVMA)","issue":"9","license":[{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ajvr"],"published-print":{"date-parts":[[2025,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n<jats:sec id=\"sc_a1\">\n<jats:title>Objective<\/jats:title>\n<jats:p>To develop an interferon \u03b3 (IFN-\u03b3) recall assay to detect a T-cell response following vaccination because antibody is seldom detected in \u0394<jats:italic>cps1<\/jats:italic>-vaccinated dogs.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sc_a2\">\n<jats:title>Methods<\/jats:title>\n<jats:p>Peripheral blood mononuclear cells were collected from naturally infected dogs with a history of coccidioidomycosis or dogs from a nonendemic area. Two- to 5-month-old Beagles were vaccinated 2 to 4 times up to 28 days apart with live, avirulent \u0394<jats:italic>cps1<\/jats:italic> and bled on study days 42, 68, or 90. Peripheral blood mononuclear cells were stimulated with \u0394<jats:italic>cps1<\/jats:italic> and stained to detect CD4<jats:sup>+<\/jats:sup> T-cell IFN-\u03b3 expression. The percentage of CD4<jats:sup>+<\/jats:sup>IFN-\u03b3<jats:sup>+<\/jats:sup> T cells compared to unstimulated baseline was calculated for each dog.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sc_a3\">\n<jats:title>Results<\/jats:title>\n<jats:p>All 5 naturally infected dogs with coccidioidomycosis had T-cell IFN-\u03b3 responses, and the 2 unexposed nonendemic dogs did not. Fourteen of 15 dogs vaccinated with \u0394<jats:italic>cps1<\/jats:italic> had recall IFN-\u03b3 responses. Subcutaneously vaccinated dogs (n = 5) had a mean 1.85-fold increase in IFN-\u03b3 over baseline, whereas IM-vaccinated dogs (n = 10) were a mean of 6- to 10-fold higher. The percentage of CD4<jats:sup>+<\/jats:sup>IFN-\u03b3<jats:sup>+<\/jats:sup> cells was higher from restimulated cells compared to baseline in both SC- and IM-vaccinated dogs (SC twice [n = 5]: 95% CI, 0.001 to 0.543; IM twice [n = 5]: 95% CI, 0.9734 to 1.948; IM 4 times [n = 5]: 95% CI, 1.207 to 5.083).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sc_a4\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>The T-cell IFN-\u03b3 recall assay of peripheral blood mononuclear cells from vaccinated dogs detects a cell-mediated immune response to the \u0394<jats:italic>cps1<\/jats:italic> vaccine.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sc_a5\">\n<jats:title>Clinical Relevance<\/jats:title>\n<jats:p>This assay has potential utility as a surrogate marker for vaccine-induced immunity.<\/jats:p>\n<\/jats:sec>","DOI":"10.2460\/ajvr.25.04.0119","type":"journal-article","created":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T09:00:09Z","timestamp":1749027609000},"source":"Crossref","is-referenced-by-count":1,"title":["Recall interferon-\u03b3 responses against Coccidioides are a surrogate marker for vaccine response in dogs"],"prefix":"10.2460","volume":"86","author":[{"given":"Lisa F.","family":"Shubitz","sequence":"first","affiliation":[{"name":"Valley Fever Center for Excellence, College of Medicine, University of Arizona, Tucson, AZ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel A.","family":"Powell","sequence":"additional","affiliation":[{"name":"Valley Fever Center for Excellence, College of Medicine, University of Arizona, Tucson, AZ"},{"name":"BIO5 Institute, University of Arizona, Tucson, AZ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5019-7567","authenticated-orcid":true,"given":"Christine D.","family":"Butkiewicz","sequence":"additional","affiliation":[{"name":"Valley Fever Center for Excellence, College of Medicine, University of Arizona, Tucson, AZ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey A.","family":"Frelinger","sequence":"additional","affiliation":[{"name":"Valley Fever Center for Excellence, College of Medicine, University of Arizona, Tucson, AZ"},{"name":"Department of Immunobiology, College of Medicine, University of Arizona, Tucson, AZ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John N.","family":"Galgiani","sequence":"additional","affiliation":[{"name":"Valley Fever Center for Excellence, College of Medicine, University of Arizona, Tucson, AZ"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1272","reference":[{"issue":"3","key":"B1","series-title":"Infect Immun","first-page":"657","article-title":"An immunoreactive, water-soluble conidial wall fraction of Coccidioides immitis","volume":"55","author":"Cole GT","year":"1987","unstructured":"Cole GT, Kirkland TN, Sun SH. An immunoreactive, water-soluble conidial wall fraction of Coccidioides immitis. Infect Immun. 1987;55(3):657\u2013667. doi:10.1128\/iai.55.3.657-667.1987"},{"key":"B2","series-title":"Med Mycol","first-page":"S30","article-title":"Update on the epidemiology of coccidioidomycosis in the United States","volume":"57","author":"McCotter OZ","year":"2019","unstructured":"McCotter OZ, Benedict K, Engelthaler DM, et al. Update on the epidemiology of coccidioidomycosis in the United States. Med Mycol. 2019;57(suppl 1):S30\u2013S40. doi:10.1093\/mmy\/myy095"},{"issue":"8","key":"B3","series-title":"J Fungi (Basel)","first-page":"838","article-title":"Vaccines to prevent coccidioidomycosis: a gene-deletion mutant of Coccidioides Posadasii as a viable candidate for human trials","volume":"8","author":"Galgiani JN","year":"2022","unstructured":"Galgiani JN, Shubitz LF, Orbach MJ, et al. Vaccines to prevent coccidioidomycosis: a gene-deletion mutant of Coccidioides Posadasii as a viable candidate for human trials. J Fungi (Basel). 2022;8(8):838. doi:10.3390\/jof8080838"},{"issue":"10","key":"B4","series-title":"Infect Immun","first-page":"3007","article-title":"A Coccidioides posadasii CPS1 deletion mutant is avirulent and protects mice from lethal infection","volume":"84","author":"Narra HP","year":"2016","unstructured":"Narra HP, Shubitz LF, Mandel MA, et al. A Coccidioides posadasii CPS1 deletion mutant is avirulent and protects mice from lethal infection. Infect Immun. 2016;84(10):3007\u20133016. doi:10.1128\/IAI.00633-16"},{"issue":"47","key":"B5","series-title":"Vaccine","first-page":"6894","article-title":"\u0394cps1 vaccine protects dogs against experimentally induced coccidioidomycosis","volume":"39","author":"Shubitz LF","year":"2021","unstructured":"Shubitz LF, Robb EJ, Powell DA, et al. \u0394cps1 vaccine protects dogs against experimentally induced coccidioidomycosis. Vaccine. 2021;39(47):6894\u20136901. doi:10.1016\/j.vaccine.2021.10.029"},{"issue":"5","key":"B6","series-title":"J Fungi (Basel)","first-page":"307","article-title":"Discovery of a unique set of dog-seroreactive Coccidioides proteins using nucleic acid programmable protein array","volume":"10","author":"Koehler MA","year":"2024","unstructured":"Koehler MA, Song L, Grill FJ, et al. Discovery of a unique set of dog-seroreactive Coccidioides proteins using nucleic acid programmable protein array. J Fungi (Basel). 2024;10(5):307. doi:10.3390\/jof10050307"},{"issue":"10","key":"B7","series-title":"Cytometry A","first-page":"1024","article-title":"OMIP-065: dog immunophenotyping and T-cell activity evaluation with a 14-color panel","volume":"97","author":"Pantelyushin S","year":"2020","unstructured":"Pantelyushin S, Ranninger E, Bettschart-Wolfensberger R, Vom Berg J. OMIP-065: dog immunophenotyping and T-cell activity evaluation with a 14-color panel. Cytometry A. 2020;97(10):1024\u20131027. doi:10.1002\/cyto.a.24168"},{"issue":"1","key":"B8","series-title":"Sci Rep","first-page":"2207","article-title":"Direct comparison of canine and human immune responses using transcriptomic and functional analyses","volume":"14","author":"Chow L","year":"2024","unstructured":"Chow L, Wheat W, Ramirez D, Impastato R, Dow S. Direct comparison of canine and human immune responses using transcriptomic and functional analyses. Sci Rep. 2024;14(1):2207. doi:10.1038\/s41598-023-50340-9"},{"issue":"suppl 1","key":"B9","series-title":"Biomarkers","first-page":"50","article-title":"Biomarkers and assessment of vaccine responses","volume":"10","author":"Hogrefe WR","year":"2005","unstructured":"Hogrefe WR. Biomarkers and assessment of vaccine responses. Biomarkers. 2005;10(suppl 1):50\u201357. doi:10.1080\/13547500500216629"},{"issue":"3","key":"B10","series-title":"Clin Microbiol Rev","first-page":"247","article-title":"Serology of coccidioidomycosis","volume":"3","author":"Pappagianis D","year":"1990","unstructured":"Pappagianis D, Zimmer BL. Serology of coccidioidomycosis. Clin Microbiol Rev. 1990;3(3):247\u2013268. doi:10.1128\/CMR.3.3.247"},{"issue":"5","key":"B11","series-title":"J Fungi","first-page":"377","article-title":"The known unknowns of the immune response to Coccidioides","volume":"7","author":"Ward RA","year":"2021","unstructured":"Ward RA, Thompson GR, Villani AC, et al. The known unknowns of the immune response to Coccidioides. J Fungi. 2021;7(5):377. doi:10.3390\/jof7050377"},{"key":"B12","series-title":"Med Mycol","first-page":"S85","article-title":"A review of innate and adaptive immunity to coccidioidomycosis","volume":"57","author":"Hung CY","year":"2019","unstructured":"Hung CY, Hsu AP, Holland SM, Fierer J. A review of innate and adaptive immunity to coccidioidomycosis. Med Mycol. 2019;57(suppl 1):S85\u2013S92. doi:10.1093\/mmy\/myy146"},{"issue":"3","key":"B13","series-title":"J Fungi","first-page":"173","article-title":"The host response to coccidioidomycosis","volume":"10","author":"Kirkland TN","year":"2024","unstructured":"Kirkland TN, Hung CY, Shubitz LF, Beyhan S, Fierer J. The host response to coccidioidomycosis. J Fungi. 2024;10(3):173. doi:10.3390\/jof10030173"},{"issue":"6","key":"B14","series-title":"Clin Diagn Lab Immunol","first-page":"700","article-title":"Preliminary evaluation of whole-blood gamma interferon release for clinical assessment of cellular immunity in patients with active coccidioidomycosis","volume":"12","author":"Ampel NM","year":"2005","unstructured":"Ampel NM, Nelson DK, Chavez S, et al. Preliminary evaluation of whole-blood gamma interferon release for clinical assessment of cellular immunity in patients with active coccidioidomycosis. Clin Diagn Lab Immunol. 2005;12(6):700\u2013704. doi:10.1128\/CDLI.12.6.700-704.2005"},{"issue":"11","key":"B15","series-title":"Infect Immun","first-page":"4483","article-title":"In vitro modulation of proliferation and cytokine production by human peripheral blood mononuclear cells from subjects with various forms of coccidioidomycosis","volume":"65","author":"Ampel NM","year":"1997","unstructured":"Ampel NM, Christian L. In vitro modulation of proliferation and cytokine production by human peripheral blood mononuclear cells from subjects with various forms of coccidioidomycosis. Infect Immun. 1997;65(11):4483\u20134487. doi:10.1128\/iai.65.11.4483-4487.1997"},{"issue":"5","key":"B16","series-title":"Clin Diagn Lab Immunol","first-page":"1039","article-title":"In vitro whole-blood analysis of cellular immunity in patients with active coccidioidomycosis by using the antigen preparation T27K","volume":"9","author":"Ampel NM","year":"2002","unstructured":"Ampel NM, Kramer LA, Li L, et al. In vitro whole-blood analysis of cellular immunity in patients with active coccidioidomycosis by using the antigen preparation T27K. Clin Diagn Lab Immunol. 2002;9(5):1039\u20131043. doi:10.1128\/CDLI.9.5.1039-1043.2002"},{"issue":"8","key":"B17","series-title":"Clin Vaccine Immunol","first-page":"917","article-title":"Cytokine profiles from antigen-stimulated whole-blood samples among patients with pulmonary or nonmeningeal disseminated coccidioidomycosis","volume":"22","author":"Ampel NM","year":"2015","unstructured":"Ampel NM, Nesbit LA, Nguyen CT, et al. Cytokine profiles from antigen-stimulated whole-blood samples among patients with pulmonary or nonmeningeal disseminated coccidioidomycosis. Clin Vaccine Immunol. 2015;22(8):917\u2013922. doi:10.1128\/CVI.00280-15"},{"key":"B18","series-title":"Am Rev Respir Dis","first-page":"559","article-title":"Coccidioidomycosis: Part I","volume":"117","author":"Drutz DJ","year":"1978","unstructured":"Drutz DJ, Catanzaro A. Coccidioidomycosis: Part I. Am Rev Respir Dis. 1978;117:559\u2013585."}],"container-title":["American Journal of Veterinary Research"],"original-title":[],"link":[{"URL":"https:\/\/avmajournals.avma.org\/view\/journals\/ajvr\/86\/9\/ajvr.25.04.0119.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/avmajournals.avma.org\/downloadpdf\/journals\/ajvr\/86\/9\/ajvr.25.04.0119.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/avmajournals.avma.org\/downloadpdf\/journals\/ajvr\/86\/9\/ajvr.25.04.0119.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T12:37:03Z","timestamp":1756816623000},"score":1,"resource":{"primary":{"URL":"https:\/\/avmajournals.avma.org\/view\/journals\/ajvr\/86\/9\/ajvr.25.04.0119.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,1]]},"references-count":18,"journal-issue":{"issue":"9"},"URL":"https:\/\/doi.org\/10.2460\/ajvr.25.04.0119","relation":{},"ISSN":["0002-9645","1943-5681"],"issn-type":[{"value":"0002-9645","type":"print"},{"value":"1943-5681","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,1]]}}}