{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T14:48:27Z","timestamp":1791557307135,"version":"4.3.4"},"reference-count":100,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2017,3,16]],"date-time":"2017-03-16T00:00:00Z","timestamp":1489622400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI 14762"],"award-info":[{"award-number":["AI 14762"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Coccidioidomycosis is a fungal infection caused by Coccidioides posadasii and Coccidioides immitis. It is estimated that 150,000 new infections occur in the United States each year. The incidence of this infection continues to rise in endemic regions. There is an urgent need for the development of better therapeutic drugs and a vaccine against coccidioidomycosis. This review discusses the features of host innate and adaptive immune responses to Coccidioides infection. The focus is on the recent advances in the immune response and host-pathogen interactions, including the recognition of spherules by the host and defining the signal pathways that guide the development of the adaptive T-cell response to Coccidioides infection. Also discussed is an update on progress in developing a vaccine against these fungal pathogens.<\/jats:p>","DOI":"10.3390\/microorganisms5010013","type":"journal-article","created":{"date-parts":[[2017,3,16]],"date-time":"2017-03-16T11:24:28Z","timestamp":1489663468000},"page":"13","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Immune Response to Coccidioidomycosis and the Development of a Vaccine"],"prefix":"10.3390","volume":"5","author":[{"given":"Natalia","family":"Castro-Lopez","sequence":"first","affiliation":[{"name":"Department of Biology and South Texas Center for Emerging Infectious Diseases, University of Texas at San Antonio, San Antonio, TX 78249, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1091-3420","authenticated-orcid":false,"given":"Chiung-Yu","family":"Hung","sequence":"additional","affiliation":[{"name":"Department of Biology and South Texas Center for Emerging Infectious Diseases, University of Texas at San Antonio, San Antonio, TX 78249, USA"},{"name":"Immune Defense Core, University of Texas, San Antonio, TX 78249, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,3,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e00550-16","DOI":"10.1128\/mBio.00550-16","article-title":"Local population structure and patterns of western hemisphere dispersal for Coccidioides spp., the fungal cause of Valley fever","volume":"7","author":"Engelthaler","year":"2016","journal-title":"MBio"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1093\/cid\/ciu681","article-title":"Valley fever: Finding new places for an old disease: Coccidioides immitis found in Washington State soil associated with recent human infection","volume":"60","author":"Litvintseva","year":"2015","journal-title":"Clin. Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Szaniszlo, P.J., and Harris, J.L. (1985). Fungal Dimorphism: With Emphasis on Fungi Pathogenic for Humans, Springer.","DOI":"10.1007\/978-1-4684-4982-2"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1080\/15572536.2003.11833250","article-title":"Molecular and phenotypic description of Coccidioides posadasii sp. nov., previously recognized as the non-California population of Coccidioides immitis","volume":"94","author":"Fisher","year":"2002","journal-title":"Mycologia"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1080\/00362176285190231","article-title":"Purification of the spherule-endospore phase of Coccidioides immitis","volume":"1","author":"Levine","year":"1961","journal-title":"Sabouraudia"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"329","DOI":"10.4161\/viru.20142","article-title":"Mouse models for the study of fungal pneumonia: A collection of detailed experimental protocols for the study of Coccidioides, Cryptococcus, Fusarium, Histoplasma and combined infection due to Aspergillus-Rhizopus","volume":"3","author":"Muhammed","year":"2012","journal-title":"Virulence"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Lewis, E.R., Bowers, J.R., and Barker, B.M. (2015). Dust devil: The life and times of the fungus that causes Valley fever. PLoS Pathog., 11.","DOI":"10.1371\/journal.ppat.1004762"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e112","DOI":"10.1093\/cid\/ciw360","article-title":"Infectious Diseases Society of America (IDSA) clinical practice guideline for the treatment of coccidioidomycosis","volume":"63","author":"Galgiani","year":"2016","journal-title":"Clin. Infect. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1128\/CMR.00005-13","article-title":"Recent advances in our understanding of the environmental, epidemiological, immunological, and clinical dimensions of coccidioidomycosis","volume":"26","author":"Nguyen","year":"2013","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_10","first-page":"185","article-title":"Coccidioidomycosis: Epidemiology","volume":"5","author":"Brown","year":"2013","journal-title":"Clin. Epidemiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"70","DOI":"10.3201\/eid2101.140836","article-title":"Rates and risk factors for coccidioidomycosis among prison inmates, California, USA, 2011","volume":"21","author":"Wheeler","year":"2015","journal-title":"Emerg. Infect. Dis."},{"key":"ref_12","unstructured":"MMWR (2013). Increase in reported coccidioidomycosis\u2014United States, 1998\u20132011. MMWR Morb. Mortal. Wkly. Rep., 62, 217\u2013221."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1111\/myc.12394","article-title":"Burden of serious fungal infections in Mexico","volume":"58","author":"Denning","year":"2015","journal-title":"Mycoses"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1111\/myc.12427","article-title":"The burden of serious human fungal infections in Brazil","volume":"59","author":"Giacomazzi","year":"2016","journal-title":"Mycoses"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1055\/s-0031-1295723","article-title":"Pulmonary coccidioidomycosis","volume":"32","author":"Thompson","year":"2011","journal-title":"Semin. Respir. Crit. Care Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1590","DOI":"10.3201\/eid1910.130427","article-title":"Coccidioidomycosis-associated hospitalizations, California, USA, 2000\u20132011","volume":"19","author":"Sondermeyer","year":"2013","journal-title":"Emerg. Infect. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1177\/0033354916662210","article-title":"Coccidioidomycosis-Associated Deaths in California, 2000\u20132013","volume":"131","author":"Sondermeyer","year":"2016","journal-title":"Public Health Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1093\/infdis\/147.3.372","article-title":"Coccidioidomycosis: Factors affecting the host-parasite interaction","volume":"147","author":"Drutz","year":"1983","journal-title":"J. Infect. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1038\/nrmicro.2015.21","article-title":"Interactions of fungal pathogens with phagocytes","volume":"14","author":"Erwig","year":"2016","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Lee, C.Y., Thompson, G.R., Hastey, C.J., Hodge, G.C., Lunetta, J.M., Pappagianis, D., and Heinrich, V. (2015). Coccidioides endospores and spherules draw strong chemotactic, adhesive, and phagocytic responses by individual human neutrophils. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0129522"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1128\/IAI.01066-15","article-title":"Card9- and MyD88-mediated gamma interferon and nitric oxide production is essential for resistance to subcutaneous Coccidioides posadasii infection","volume":"84","author":"Hung","year":"2016","journal-title":"Infect. Immun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1093\/infdis\/172.1.199","article-title":"Differences in oxidant release by human polymorphonuclear leukocytes produced by stimulation with different phases of Coccidioides immitis","volume":"172","author":"Galgiani","year":"1995","journal-title":"J. Infect. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2106","DOI":"10.1128\/IAI.01579-13","article-title":"Interleukin-1 receptor but not Toll-like receptor 2 is essential for MyD88-dependent Th17 immunity to Coccidioides infection","volume":"82","author":"Hung","year":"2014","journal-title":"Infect. Immun."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1016\/j.ajpath.2016.02.001","article-title":"Neutrophil-epithelial interactions: A double-edged sword","volume":"186","author":"Parkos","year":"2016","journal-title":"Am. J. Pathol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/j.it.2004.09.015","article-title":"The chemokine system in diverse forms of macrophage activation and polarization","volume":"25","author":"Mantovani","year":"2004","journal-title":"Trends Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1128\/IAI.73.3.1553-1560.2005","article-title":"Innate immunity to the pathogenic fungus Coccidioides posadasii is dependent on Toll-like receptor 2 and Dectin-1","volume":"73","author":"Viriyakosol","year":"2005","journal-title":"Infect. Immun."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e00597-12","DOI":"10.1128\/mBio.00597-12","article-title":"Dectin-1 is required for resistance to coccidioidomycosis in mice","volume":"4","author":"Viriyakosol","year":"2013","journal-title":"MBio"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1128\/iai.39.3.1201-1207.1983","article-title":"Activation of macrophages by lymphokines: Enhancement of phagosome-lysosome fusion and killing of Coccidioides immitis","volume":"39","author":"Beaman","year":"1983","journal-title":"Infect. Immun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"4227","DOI":"10.1128\/iai.59.11.4227-4229.1991","article-title":"Effects of recombinant gamma interferon and tumor necrosis factor on in vitro interactions of human mononuclear phagocytes with Coccidioides immitis","volume":"59","author":"Beaman","year":"1991","journal-title":"Infect. Immun."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4511","DOI":"10.1128\/IAI.05726-11","article-title":"Vaccine immunity to coccidioidomycosis occurs by early activation of three signal pathways of T helper cell response (Th1, Th2, and Th17)","volume":"79","author":"Hung","year":"2011","journal-title":"Infect. Immun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.micpath.2011.03.013","article-title":"Nitric oxide synthase activity has limited influence on the control of Coccidioides infection in mice","volume":"51","author":"Gonzalez","year":"2011","journal-title":"Microb. Pathog."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1016\/j.micpath.2011.08.003","article-title":"Absence of phagocyte NADPH oxidase 2 leads to severe inflammatory response in lungs of mice infected with Coccidioides","volume":"51","author":"Gonzalez","year":"2011","journal-title":"Microb. Pathog."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Margolis, D.A., Viriyakosol, S., Fierer, J., and Kirkland, T.N. (2011). The role of reactive oxygen intermediates in experimental coccidioidomycois in mice. BMC Microbiol., 11.","DOI":"10.1186\/1471-2180-11-71"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2695","DOI":"10.1128\/iai.56.10.2695-2701.1988","article-title":"Immunoreactivity of a surface wall fraction produced by spherules of Coccidioides immitis","volume":"56","author":"Cole","year":"1988","journal-title":"Infect. Immun."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3443","DOI":"10.1128\/IAI.70.7.3443-3456.2002","article-title":"A parasitic phase-specific adhesin of Coccidioides immitis contributes to the virulence of this respiratory Fungal pathogen","volume":"70","author":"Hung","year":"2002","journal-title":"Infect. Immun."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"6689","DOI":"10.1128\/IAI.73.10.6689-6703.2005","article-title":"A metalloproteinase of Coccidioides posadasii contributes to evasion of host detection","volume":"73","author":"Hung","year":"2005","journal-title":"Infect. Immun."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.micpath.2010.11.006","article-title":"Coccidioides releases a soluble factor that suppresses nitric oxide production by murine primary macrophages","volume":"50","author":"Gonzalez","year":"2011","journal-title":"Microb. Pathog."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/j.chom.2012.04.005","article-title":"Dendritic cells in antifungal immunity and vaccine design","volume":"11","author":"Roy","year":"2012","journal-title":"Cell Host Microbe"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1086\/323664","article-title":"Dendritic cells pulsed with Coccidioides immitis lysate induce antigen-specific naive T cell activation","volume":"184","author":"Richards","year":"2001","journal-title":"J. Infect. Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2415","DOI":"10.1128\/IAI.74.4.2415-2422.2006","article-title":"Spherules derived from Coccidioides posadasii promote human dendritic cell maturation and activation","volume":"74","author":"Dionne","year":"2006","journal-title":"Infect. Immun."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2020","DOI":"10.4049\/jimmunol.169.4.2020","article-title":"Reversal of coccidioidal anergy in vitro by dendritic cells from patients with disseminated coccidioidomycosis","volume":"169","author":"Richards","year":"2002","journal-title":"J. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3900","DOI":"10.4049\/jimmunol.175.6.3900","article-title":"Efficacy of antigen 2\/proline-rich antigen cDNA-transfected dendritic cells in immunization of mice against Coccidioides posadasii","volume":"175","author":"Awasthi","year":"2005","journal-title":"J. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Vilekar, P., Awasthi, V., Lagisetty, P., King, C., Shankar, N., and Awasthi, S. (2010). In vivo trafficking and immunostimulatory potential of an intranasally-administered primary dendritic cell-based vaccine. BMC Immunol., 11.","DOI":"10.1186\/1471-2172-11-60"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/s00281-014-0462-4","article-title":"Pattern recognition receptors in antifungal immunity","volume":"37","author":"Plato","year":"2015","journal-title":"Semin. Immunopathol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.4049\/jimmunol.1302314","article-title":"C-type lectin receptors differentially induce Th17 cells and vaccine immunity to the endemic mycosis of North America","volume":"192","author":"Wang","year":"2014","journal-title":"J. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1038\/gene.2008.23","article-title":"Susceptibility to Coccidioides species in C57BL\/6 mice is associated with expression of a truncated splice variant of Dectin-1 (Clec7a)","volume":"9","author":"Viriyakosol","year":"2008","journal-title":"Genes Immun."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1128\/IAI.01355-13","article-title":"Neither dectin-2 nor the mannose receptor is required for resistance to Coccidioides immitis in mice","volume":"82","author":"Viriyakosol","year":"2014","journal-title":"Infect. Immun."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"470","DOI":"10.3109\/13693780903226019","article-title":"Susceptibility of TLR4-defective C3H\/HeJ mice to Coccidioides posadasii infection","volume":"48","author":"Awasthi","year":"2010","journal-title":"Med. Mycol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e85","DOI":"10.1038\/cti.2016.22","article-title":"Toll-like receptors: The swiss army knife of immunity and vaccine development","volume":"5","author":"Dowling","year":"2016","journal-title":"Clin. Transl. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1086\/502972","article-title":"Both CD4+ and CD8+ T cells can mediate vaccine-induced protection against Coccidioides immitis infection in mice","volume":"193","author":"Fierer","year":"2006","journal-title":"J. Infect. Dis."},{"key":"ref_51","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":"Wuthrich","year":"2003","journal-title":"J. Exp. Med."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Nanjappa, S.G., Heninger, E., Wuthrich, M., Gasper, D.J., and Klein, B.S. (2012). Tc17 cells mediate vaccine immunity against lethal fungal pneumonia in immune deficient hosts lacking CD4+ T cells. PLoS Pathog., 8.","DOI":"10.1371\/journal.ppat.1002771"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1172\/JCI58762","article-title":"Protective antifungal memory CD8+ T cells are maintained in the absence of CD4+ T cell help and cognate antigen in mice","volume":"122","author":"Nanjappa","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1126\/science.1178334","article-title":"Mechanisms underlying lineage commitment and plasticity of helper CD4+ T cells","volume":"327","author":"Paul","year":"2010","journal-title":"Science"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"521957","DOI":"10.1155\/2015\/521957","article-title":"Functional and phenotypic plasticity of CD4+ T cell subsets","volume":"2015","author":"Caza","year":"2015","journal-title":"Biomed. Res. Int."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1128\/CMR.17.4.804-839.2004","article-title":"Coccidioidomycosis: Host response and vaccine development","volume":"17","author":"Cox","year":"2004","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1080\/13693780410001687349","article-title":"A vaccine against coccidioidomycosis is justified and attainable","volume":"42","author":"Cole","year":"2004","journal-title":"Med. Mycol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"3535","DOI":"10.1016\/j.vaccine.2005.01.147","article-title":"Immune response of vaccinated and non-vaccinated mice to Coccidioides posadasii infection","volume":"23","author":"Xue","year":"2005","journal-title":"Vaccine"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2878","DOI":"10.1128\/IAI.69.5.2878-2887.2001","article-title":"Recombinant urease and urease DNA of Coccidioides immitis elicit an immunoprotective response against coccidioidomycosis in mice","volume":"69","author":"Li","year":"2001","journal-title":"Infect. Immun."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"5553","DOI":"10.1128\/IAI.00885-08","article-title":"Vaccine-induced cellular immune responses differ from innate responses in susceptible and resistant strains of mice infected with Coccidioides posadasii","volume":"76","author":"Shubitz","year":"2008","journal-title":"Infect. Immun."},{"key":"ref_61","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":"ref_62","doi-asserted-by":"crossref","first-page":"5288","DOI":"10.4049\/jimmunol.175.8.5288","article-title":"IL-12 is required for induction but not maintenance of protective, memory responses to Blastomyces dermatitidis: Implications for vaccine development in immune-deficient hosts","volume":"175","author":"Wuthrich","year":"2005","journal-title":"J. Immunol."},{"key":"ref_63","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":"Wuthrich","year":"2002","journal-title":"J. Immunol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/S0923-2494(98)80765-7","article-title":"Protective immunity in coccidioidomycosis: The life cycle and biology of Coccidioides immitis","volume":"149","author":"Cox","year":"1998","journal-title":"Res. Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"3196","DOI":"10.1128\/IAI.00459-09","article-title":"A genetically engineered live attenuated vaccine of Coccidioides posadasii protects BALB\/c mice against coccidioidomycosis","volume":"77","author":"Xue","year":"2009","journal-title":"Infect. Immun."},{"key":"ref_66","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":"Wuthrich","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.4049\/jimmunol.1100921","article-title":"A TCR transgenic mouse reactive with multiple systemic dimorphic fungi","volume":"187","author":"Wuthrich","year":"2011","journal-title":"J. Immunol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"4681","DOI":"10.1016\/j.vaccine.2012.04.084","article-title":"An agonist of human complement fragment C5a enhances vaccine immunity against Coccidioides infection","volume":"30","author":"Hung","year":"2012","journal-title":"Vaccine"},{"key":"ref_69","first-page":"151","article-title":"Coccidioides immitis in patients with human immunodeficiency virus infections","volume":"5","author":"Galgiani","year":"1990","journal-title":"Semin. Respir. Infect."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1128\/CVI.00280-15","article-title":"Cytokine profiles from antigen-stimulated whole-blood samples among patients with pulmonary or nonmeningeal disseminated coccidioidomycosis","volume":"22","author":"Ampel","year":"2015","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"e99","DOI":"10.1093\/cid\/ciq215","article-title":"Interleukin-12 receptor beta1 deficiency predisposing to disseminated coccidioidomycosis","volume":"52","author":"Vinh","year":"2011","journal-title":"Clin. Infect. Dis."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1624","DOI":"10.1016\/j.jaci.2013.01.052","article-title":"Signal transducer and activator of transcription 1 (STAT1) gain-of-function mutations and disseminated coccidioidomycosis and histoplasmosis","volume":"131","author":"Sampaio","year":"2013","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1635","DOI":"10.1084\/jem.20110958","article-title":"Gain-of-function human STAT1 mutations impair IL-17 immunity and underlie chronic mucocutaneous candidiasis","volume":"208","author":"Liu","year":"2011","journal-title":"J. Exp. Med."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1055\/s-2008-1063855","article-title":"Pulmonary coccidioidomycosis","volume":"29","author":"Spinello","year":"2008","journal-title":"Semin. Respir. Crit. Care Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"4975","DOI":"10.1016\/j.vaccine.2013.08.007","article-title":"First-in-human evaluation of genetically attenuated Plasmodium falciparum sporozoites administered by bite of Anopheles mosquitoes to adult volunteers","volume":"31","author":"Spring","year":"2013","journal-title":"Vaccine"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1007\/s12281-012-0105-y","article-title":"Progress toward a human vaccine against coccidioidomycosis","volume":"6","author":"Cole","year":"2012","journal-title":"Curr. Fungal Infect. Rep."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Cole, G.T., Hung, C.Y., Sanderson, S.D., Hurtgen, B.J., Wuthrich, M., Klein, B.S., Deepe, G.S., Ostroff, G.R., and Levitz, S.M. (2013). Novel strategies to enhance vaccine immunity against coccidioidomycosis. PLoS Pathog., 9.","DOI":"10.1371\/journal.ppat.1003768"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1128\/IAI.67.2.630-635.1999","article-title":"Genetic vaccination against Coccidioides immitis: Comparison of vaccine efficacy of recombinant antigen 2 and antigen 2 cDNA","volume":"67","author":"Jiang","year":"1999","journal-title":"Infect. Immun."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"3287","DOI":"10.1128\/IAI.70.6.3287-3289.2002","article-title":"Protection of mice against Coccidioides immitis intranasal infection by vaccination with recombinant antigen 2\/PRA","volume":"70","author":"Shubitz","year":"2002","journal-title":"Infect. Immun."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2935","DOI":"10.1128\/IAI.67.6.2935-2940.1999","article-title":"Resistance to Coccidioides immitis in mice after immunization with recombinant protein or a DNA vaccine of a proline-rich antigen","volume":"67","author":"Abuodeh","year":"1999","journal-title":"Infect. Immun."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"3994","DOI":"10.1128\/iai.63.10.3994-4002.1995","article-title":"Molecular and biochemical characterization of a Coccidioides immitis-specific antigen","volume":"63","author":"Pan","year":"1995","journal-title":"Infect. Immun."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"5904","DOI":"10.1016\/j.vaccine.2006.04.002","article-title":"Improved protection of mice against lethal respiratory infection with Coccidioides posadasii using two recombinant antigens expressed as a single protein","volume":"24","author":"Shubitz","year":"2006","journal-title":"Vaccine"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1128\/IAI.74.3.1865-1872.2006","article-title":"Protein expression profiling of Coccidioides posadasii by two-dimensional differential in-gel electrophoresis and evaluation of a newly recognized peroxisomal matrix protein as a recombinant vaccine candidate","volume":"74","author":"Orsborn","year":"2006","journal-title":"Infect. Immun."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2627","DOI":"10.1128\/iai.60.7.2627-2635.1992","article-title":"An arthroconidial-spherule antigen of Coccidioides immitis: Differential expression during in vitro fungal development and evidence for humoral response in humans after infection or vaccination","volume":"60","author":"Galgiani","year":"1992","journal-title":"Infect. Immun."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"5802","DOI":"10.1128\/IAI.00961-06","article-title":"Multivalent recombinant protein vaccine against coccidioidomycosis","volume":"74","author":"Tarcha","year":"2006","journal-title":"Infect. Immun."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1128\/IAI.74.1.516-527.2006","article-title":"A recombinant aspartyl protease of Coccidioides posadasii induces protection against pulmonary coccidioidomycosis in mice","volume":"74","author":"Tarcha","year":"2006","journal-title":"Infect. Immun."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"5777","DOI":"10.1128\/IAI.00807-07","article-title":"Evaluation of two homologous proline-rich proteins of Coccidioides posadasii as candidate vaccines against coccidioidomycosis","volume":"75","author":"Herr","year":"2007","journal-title":"Infect. Immun."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"778","DOI":"10.4161\/hv.27332","article-title":"Recent progress in adjuvant discovery for peptide-based subunit vaccines","volume":"10","author":"Azmi","year":"2014","journal-title":"Hum. Vaccine Immunother."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1016\/j.cell.2012.02.012","article-title":"Beyond empiricism: Informing vaccine development through innate immunity research","volume":"148","author":"Levitz","year":"2012","journal-title":"Cell"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1016\/j.immuni.2011.10.018","article-title":"Th17 cells mediate clade-specific, serotype-independent mucosal immunity","volume":"35","author":"Chen","year":"2011","journal-title":"Immunity"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"3960","DOI":"10.1128\/IAI.00566-12","article-title":"Construction and evaluation of a novel recombinant T cell epitope-based vaccine against coccidioidomycosis","volume":"80","author":"Hurtgen","year":"2012","journal-title":"Infect. Immun."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"312","DOI":"10.4049\/jimmunol.1200603","article-title":"Relative contributions of Dectin-1 and complement to immune responses to particulate b-glucans","volume":"189","author":"Huang","year":"2012","journal-title":"J. Immunol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1128\/CVI.00463-13","article-title":"Characterization and optimization of the glucan particle-based vaccine platform","volume":"20","author":"Huang","year":"2013","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1128\/iai.40.3.912-916.1983","article-title":"Inbred mouse strains differ in resistance to lethal Coccidioides immitis infection","volume":"40","author":"Kirkland","year":"1983","journal-title":"Infect. Immun."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"3514","DOI":"10.1128\/iai.63.9.3514-3519.1995","article-title":"Roles of gamma interferon and interleukin-4 in genetically determined resistance to Coccidioides immitis","volume":"63","author":"Magee","year":"1995","journal-title":"Infect. Immun."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1016\/j.tim.2006.07.009","article-title":"IL-10 and susceptibility to Coccidioides immitis infection","volume":"14","author":"Fierer","year":"2006","journal-title":"Trends Microbiol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"3387","DOI":"10.1128\/IAI.01985-05","article-title":"High levels of interleukin-10 impair resistance to pulmonary coccidioidomycosis in mice in part through control of nitric oxide synthase 2 expression","volume":"74","author":"Walls","year":"2006","journal-title":"Infect. Immun."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"5336","DOI":"10.1016\/j.vaccine.2016.08.078","article-title":"Preclinical identification of vaccine induced protective correlates in human leukocyte antigen expressing transgenic mice infected with Coccidioides posadasii","volume":"34","author":"Hurtgen","year":"2016","journal-title":"Vaccine"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"D784","DOI":"10.1093\/nar\/gku1166","article-title":"Allele frequency net 2015 update: New features for HLA epitopes, KIR and disease and HLA adverse drug reaction associations","volume":"43","author":"Takeshita","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Ru, Z., Xiao, W., Pajot, A., Kou, Z., Sun, S., Maillere, B., Zhao, G., Ojcius, D.M., Lone, Y.C., and Zhou, Y. (2012). Development of a humanized HLA-A2.1\/DP4 transgenic mouse model and the use of this model to map HLA-DP4-restricted epitopes of HBV envelope protein. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0032247"}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/5\/1\/13\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:30:35Z","timestamp":1760207435000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/5\/1\/13"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,3,16]]},"references-count":100,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,3]]}},"alternative-id":["microorganisms5010013"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms5010013","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,3,16]]}}}