Coccidioides spp.
5500
The tiny spores (2 × 4 μm) convert into multinucleate round cells (spherules) within the lungs of the host and undergo isotropic growth to produce large parasitic cells (60 to > 100 μm in diameter). The latter undergo an elaborate process of wall growth and cytoplasmic compartmentalization to form and release a multitude of endospores (4–10 μm in diameter). Each endospore grows and differentiates into a second-generation spherule, which is again able to yield an average of 200 to 300 endospores. Mature spherules most likely escape phagocytosis simply because they are too large to be ingested by neutrophils, macrophages, and dendritic cells (Hung et al., 2007).
Coccidioidomycosis (California disease, Desert rheumatism, San Joaquin valley fever, and Valley fev
Both clinical and experimental evidence have demonstrated that T-cell immunity is pivotal for defense against this respiratory disease. The ability of the host to elicit a strong delayed-type hypersensitivity response to the pathogen is essential (Tarcha et al., 2006).
Coccidiomycosis is mainly a disease of immunocompromised in humans, but mice and monkeys have been used as animal models of disease (Ivey et al., 2003).
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).
Baboon
Papio cynocephalus
9556
Bank vole
Clethrionomys glareolus
447135
Bear
Ursus americanus
9643
Birds
Passeroidea
175121
Brown Trout
Salmo trutta
8032
Buffalo
Bison bison
9901
Carnivores
Vulpes
9625
Cat
Felis catus
9685
Catfishes
Siluriformes
7995
Cattle
Bos taurus
9913
Chicken
Gallus gallus
9031
Chimpanzee
Pan troglodytes
9598
chinchillas
Chinchillidae
10150
Copper Pheasant
Syrmaticus soemmerringii
9067
Deer
Cervus elaphus
9860
Deer mouse
Peromyscus maniculatus
10042
Dog
Canis familiaris
9615
Ducks
Anas
8835
Ferret
Mustela putorius furo
9669
Fish
Hyperotreti
117565
Gerbil
Gerbillina
10045
Goat
Capra hircus
9925
Gray wolf
Canis lupus
9612
Guinea pig
Cavia porcellus
10141
Hamster
Mesocricetus auratus
10036
Horse
Equus caballus
9796
Human
Homo sapiens
9606
Macaque
Macaca fascicularis
9541
Mongolian Gerbil
Meriones unguiculatus
10047
Monkey
Platyrrhini
9479
Mouse
Mus musculus
10090
None
None
Parrot
Psittacidae
9224
Pig
Sus scrofa
9823
Rabbit
Oryctolagus cuniculus
9986
Rainbow trout
Oncorhynchus mykiss
8022
Rat
Rattus
10114
Raven
Corvus corax
56781
sei whale
Balaenoptera borealis
9768
Sheep
Ovis aries
9940
Squirrel
Spermophilus richardsonii
37591
Tree shrew
Tupaiidae
9393
Trouts, salmons & chars
Salmoninae
504568
Turkey
Meleagris gallopavo
9103
Vole
Microtus ochrogaster
79684
Water buffalo
Bubalus bubalis
391902
C. immitis Subunit URE Protein Vaccine
VO_0011463
Subunit vaccine
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
DNA vaccine
Research
pVR1012 [Ref1392:Awasthi et al., 2005]
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
Subunit vaccine
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
Subunit vaccine
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:304882
199306
?
glucanosyltransferase
8.01
15771.51
231
Glycosyl hydrolase family 1; cl23725
>AAK69492.1 glucanosyltransferase, partial [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:239311
199306
?
peroxisomal matrix protein
5.21
16731.65
234
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
>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:128986
CDD:282710
5501
?
proline-rich antigen
3.93
18554.97
254
eight cysteine-containing domain present in fungal extracellular membrane proteins; smart00747
>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:294200
5501
?
urease
4.18
15939.32
219
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 a...; cl00281
>BAE20261.1 urease, partial [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].
Awasthi et al., 2005
journal
Awasthi S, Awasthi V, Magee DM, Coalson JJ
Efficacy of antigen 2/proline-rich antigen cDNA-transfected dendritic cells in immunization of mice against Coccidioides posadasii
2005
175
6
3900-3906
Journal of immunology (Baltimore, Md. : 1950)
Delgado et al., 2003
journal
Delgado N, Xue J, Yu JJ, Hung CY, Cole GT
A recombinant beta-1,3-glucanosyltransferase homolog of Coccidioides posadasii protects mice against coccidioidomycosis
2003
71
6
3010-3019
Infection and immunity
Hung et al., 2007
journal
Hung CY, Xue J, Cole GT
Virulence mechanisms of coccidioides
2007
1111
225-235
Annals of the New York Academy of Sciences
Ivey et al., 2003
journal
Ivey FD, Magee DM, Woitaske MD, Johnston SA, Cox RA
Identification of a protective antigen of Coccidioides immitis by expression library immunization
2003
21
27-30
4359-4367
Vaccine
Kirkland et al., 1998
journal
Kirkland TN, Thomas PW, Finley F, Cole GT
Immunogenicity of a 48-kilodalton recombinant T-cell-reactive protein of Coccidioides immitis
1998
66
2
424-431
Infection and immunity
Li et al., 2001
journal
Li K, Yu JJ, Hung CY, Lehmann PF, Cole GT
Recombinant urease and urease DNA of Coccidioides immitis elicit an immunoprotective response against coccidioidomycosis in mice
2001
69
5
2878-2887
Infection and immunity
Orsborn et al., 2006
journal
Orsborn KI, Shubitz LF, Peng T, Kellner EM, Orbach MJ, Haynes PA, Galgiani JN
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
2006
74
3
1865-1872
Infection and immunity
Tarcha et al., 2006a
journal
Tarcha EJ, Basrur V, Hung CY, Gardner MJ, Cole GT
A recombinant aspartyl protease of Coccidioides posadasii induces protection against pulmonary coccidioidomycosis in mice
2006
74
1
516-527
Infection and immunity
Tarcha et al., 2006b
journal
Tarcha EJ, Basrur V, Hung CY, Gardner MJ, Cole GT
Multivalent recombinant protein vaccine against coccidioidomycosis
2006
74
10
5802-5813
Infection and immunity