Coccidioides spp. 5500 Coccidioidomycosis (California disease, Desert rheumatism, San Joaquin valley fever, and Valley fev Coccidioidomycosis is a human respiratory disease caused by inhalation of airborne spores produced by Coccidioides spp (Coccidioides immitis and C. posadasii). The pathogen is an anamorphic (asexual) ascomycetous fungus which resides in alkaline desert and semidesert soil in regions of the southwestern United States. The major areas where this disease is endemic include some of the most rapidly growing communities of Arizona and southern California. People who are frequently exposed to dust from the soil in these regions have a high chance of infection with Coccidioides. Recurrent epidemics of coccidioidomycosis appear to be correlated with climatic conditions. Periods of rain in the spring enhance growth of the soilborne saprobic phase of Coccidioides, which results in “blooms” of spores that are air dispersed during the late fall and winter seasons. Risk factors known to contribute to symptomatic coccidioidal infection include pregnancy (third trimester), immunosuppression, age (>65 years), and racial or geographic origin. Antifungal drug therapy for coccidioidomycosis (e.g., amphotericin B, fluconazole, or intraconazole) is typically continued for many months to years. Persons who contract coccidioidal meningitis require lifelong therapy. Coccidioides infection can be life threatening and, at the very least, is responsible for high medical costs incurred by patients as a result of hospitalization, clinic visits, lost wages, and long-term drug therapy (Tarcha et al., 2006). Cattle Bos taurus 9913 Chicken Gallus gallus 9031 chinchillas Chinchillidae 10150 Copper Pheasant Syrmaticus soemmerringii 9067 Deer mouse Peromyscus maniculatus 10042 Ducks Anas 8835 Ferret Mustela putorius furo 9669 Goat Capra hircus 9925 Guinea pig Cavia porcellus 10141 Hamster Mesocricetus auratus 10036 Horse Equus caballus 9796 Human Homo sapiens 9606 Monkey Platyrrhini 9479 Mouse Mus musculus 10090 Pig Sus scrofa 9823 Rabbit Oryctolagus cuniculus 9986 Rat Rattus 10114 Raven Corvus corax 56781 Sheep Ovis aries 9940 Vole Microtus ochrogaster 79684 C. immitis Subunit URE Protein Vaccine VO_0011463 Research Subcutaneous injection CpG ODN (Li et al., 2001) Subcutaneous injection Recombinant protein preparation BALB/c Mice each were immunized s.c. with recombinant protein (15 μg of rURE) or bovine serum albumin for control group (Li et al., 2001). The rURE-immune mice showed significantly lower counts of C. immitis in both lungs and spleens compared to control mice immunized with BSA plus CpG ODN (Li et al., 2001). Mice were challenged by the i.p. route at 14 days after the last protein immunization or 30 days after the last DNA immunization. The inoculum contained 100 viable arthroconidia in 100 μl of PBS (Li et al., 2001). C. posadasii DNA Vaccine encoding PRA Protein VO_0011461 Research Intramuscular injection (i.m.) Intramuscular injection (i.m.) DNA vaccine construction C57BL6 C57BL6 mice were anesthetized by i.m. injection of ketamine-xylazine (75 µg/g and 10 µg/g body weight, respectively). Transfected DCs (1–1.5 x 10^6 per 30 µl) were intranasally administered in both nares alternately. Comparative controls were Ag2/PRA plasmid DNA alone, nontransfected cells, and cells transfected with the vector plasmid alone. The immunization was performed twice at an interval of 1 wk (on days 0 and 7). The second immunization was given to boost the immune response (Awasthi et al., 2005). Upon necropsy after 10 days of infection, fungal burden in lung and spleen of immunized mice was significantly reduced as compared with the control animals. The lung tissue homogenates of immunized animals showed higher levels of IFN-gamma. Histologically, lung tissues of immunized mice were in better condition than the control mice (Awasthi et al., 2005). The immunized mice were infected with C. posadasii either i.p. or intranasally. Intranasal challenge was given on day 19 with 30 arthroconidia per 30 µl of saline, whereas the i.p. challenge was given on day 14 with 2500 arthroconidia per 500 µl of saline. The infected mice become symptomatic around day 9–10 and start dying on day 11. Therefore, the mice were sacrificed on 10th day of infection, and their lungs and spleens were collected (Awasthi et al., 2005). C. posadasii Subunit GEL1 Protein Vaccine VO_0011490 Research Intraperitoneal injection (i.p.) CpG ODN (Integrated DNA Technologies, Inc., Coralville, Iowa) (Delgado et al., 2003). Intraperitoneal injection (i.p.) Recombinant protein preparation BALB/c, C57BL/6 Mice were immunized subcutaneously (s.c.) with rGel1p plus adjuvant. The mice were then boosted by s.c. immunization 14 days later with the same amount of immunogen plus adjuvant (Delgado et al., 2003). rGel1p-immune mice infected with the pathogen showed a significant reduction in fungal burden and increased survival compared to nonimmune mice (Delgado et al., 2003). The animals were subsequently challenged with 100 viable arthroconidia by the i.p. route 2 weeks after the last immunization and then sacrificed 12 days later to determine the residual CFU in the lungs and spleen (Delgado et al., 2003). C. posadasii Subunit PMP1 Protein Vaccine VO_0011460 Research Intramuscular injection (i.m.) Monophosphoryl lipid A-stable emulsion (MPL-SE) adjuvant (Orsborn et al., 2006). Intramuscular injection (i.m.) Recombinant protein preparation C57BL/6 Mice were immunized subcutaneously with 1, 5, or 50 μg rPmp1 with monophosphoryl lipid A-stable emulsion (MPL-SE) adjuvant on day 0 and day 14. Control mice received adjuvant only (Orsborn et al., 2006). Vaccination with PMP1 elicited significant protection in mice and a reduction in colonization of organs by Coccidioides (Orsborn et al., 2006). Four weeks after boosting (day 42), the mice were infected intraperitoneally with 310 arthroconidia and sacrificed 2 weeks later (Orsborn et al., 2006). GEL1 Coccidioides posadasii VO_0011330 14582416 CDD:159804 199306 ? glucanosyltransferase 159 Cellulase (glycosyl hydrolase family 5); cl12144 >gi|14582416|gb|AAK69492.1|AF280397_1 glucanosyltransferase [Coccidioides posadasii] SGGLVYEYPQEPSNYGLVQLGKGKPKELDDFKALAKAFKGTKNPSGDGGYNSTGGANPCPKKNAPNWDVD SESLPAIPEPAKKFMKDGPGEGPGLSGKGSQNAGTQSSGTATPGSGSVDPTSSAGAAAGLRPEFGIAPMM CAMLVVLSSMFGASFIFMV Protective antigen The GEL1 mRNA of C. posadasii was detected at the highest level during the endosporulation stage of the parasitic cycle, and the mature protein was immunolocalized to the surface of endospores. BALB/c or C57BL/6 mice were immunized subcutaneously with the bacterium-expressed recombinant protein (rGel1p) to evaluate its protective efficacy against a lethal challenge of C. posadasii by either the intraperitoneal or intranasal route. In both cases, rGel1p-immune mice infected with the pathogen showed a significant reduction in fungal burden and increased survival compared to nonimmune mice [Ref1389:Delgado et al., 2003]. Pmp1 Coccidioides posadasii VO_0011332 78364922 CDD:48562 199306 ? peroxisomal matrix protein 166 Peroxiredoxin (PRX) family, PRX5-like subfamily; members are similar to the human protein, PRX5, a homodimeric TRX peroxidase, widely expressed in tissues and found cellularly in mitochondria, peroxisomes and the cytosol. The cellular location of PRX5...; cd03013 >gi|78364922|gb|ABB42829.1| peroxisomal matrix protein [Coccidioides posadasii] MASLKAGDSFLSDVVFSYIPWTPDNKDIKACGMPQNYEASKLWADKKVVLFSLPGAFTPTCSASHLPGYI QKLPQLKEKGVDVVAVLAFNDAWVMSAWGKANGVTGDDILFLSDPEAKFSKSIGWNAGERTGRYAMIIDH GQVTYAEIEPGREVTVSGADAVISKL Protective antigen Recombinant Pmp1 was reactive with serum from individuals with both acute and protracted disease, and evoked protection in two murine models of infection with C. posadasii [Ref1391:Orsborn et al., 2006]. Pra Coccidioides immitis VO_0011333 42742528 CDD:155093 5501 ? proline-rich antigen 194 CFEM domain; cl02770 >gi|42742528|gb|AAS45282.1| proline-rich antigen [Coccidioides immitis] MQFSHALIALVAAGLASAQLPDIPPCALNCFVEALGNDGCTRLTDFKCHCSKPELPGQITPCVEEACPLD ARISVSNIVVDQCSKAGVPIEIPPVDTTAAPEPSETAEPTAEPTEEPTAEPTAEPTAEPTHEPTEEPTAV PTGTGGGVPTGTGSFTVTGRPTASTPAEFPGAGSNVRASVGGIAAALLGLAAYL Protective antigen C57BL6 mice were immunized with syngeneic, bone marrow-derived DCs (JAWS II cells) transfected with a cDNA encoding the protective Coccidioides-Ag2/proline-rich Ag (pra). The immunized mice were lethally challenged with C. posadasii through either an i.p. or intranasal route. Upon necropsy after 10 days of infection, fungal burden in lung and spleen of immunized mice was significantly reduced as compared with the control animals. The lung tissue homogenates of immunized animals showed higher levels of IFN-gamma. Histologically, lung tissues of immunized mice were in better condition than the control mice [Ref1392:Awasthi et al., 2005]. URE Coccidioides immitis VO_0011331 73808050 CDD:174087 CDD:30035 5501 ? urease 164 Superfamily of metallo-dependent hydrolases (also called amidohydrolase superfamily) is a large group of proteins that show conservation in their 3-dimensional fold (TIM barrel) and in details of their active site. The vast majority of the members have...; cl00281 >gi|73808050|dbj|BAE20261.1| urease [Coccidioides immitis] CGIGKAGNPDVMDGVTPNMIVGSSTDVIACEGKIVTAGGIDTHVHFICPQQVEEALASGVTTLLGGGTGP TEGTNATTCTPAPNQFKTMMQACDHLPINVGLTGKGNDSGLPSLRDQCRAGAAGLKVHEDWGATPAVIDT CLQVCDEFDIQCLIHTDTLNESGF Protective antigen Recombinant urease (rURE) of C. immitis was expressed in Escherichia coli and tested asa vaccine candidate in BALB/c mice. BALB/c mice immunized subcutaneously with rURE and subsequently challenged by the intraperitoneal (i.p.) route with a lethal inoculum of C. immitis arthroconidia demonstrated a significant reduction in the level of C. immitis infection compared to control animals [Ref1390:Li et al., 2001]. 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