Resistance to Coccidioides immitis in mice after immunization with recombinant protein or a DNA vaccine of a proline-rich antigen.
Two inbred strains of mice (BALB/c and C57BL/6) were vaccinated with either recombinant expression protein of a Coccidioides immitis spherule-derived proline-rich antigen (rPRA) in monophosphoryl lipid A-oil emulsion adjuvant or a DNA vaccine based on the same antigen. Four weeks after vaccination, mice were infected intraperitoneally with arthroconidia. By 2 weeks, groups of mice receiving saline or plasmids with no PRA insert exhibited significant weight loss, and quantitative CFUs in the lungs ranged from 5.9 to 6.4 log10. In contrast, groups of mice immunized with either rPRA or DNA vaccine had significantly smaller pulmonary fungal burdens, ranging from 3.0 to 4.5 log10 fewer CFUs. In vitro immunologic markers of lymphocyte proliferation and gamma interferon (IFN-gamma) release after splenocytes were stimulated with rPRA correlated with protection. Also, plasma concentrations of rPRA-specific total immunoglobulin G (IgG), IgG1, and IgG2a showed increases in vaccinated mice. These studies expand earlier work by demonstrating protection in mice which differ in H-2 background, by using an adjuvant that is potentially applicable to human use, and by achieving comparable protections with a DNA-based vaccine. Our in vitro results substantiate a Th1 response as evidenced by IFN-gamma release and increased IgG2a. However, IgG1 was also stimulated, suggesting some Th2 response as well. PRA is a promising vaccine candidate for prevention of coccidioidomycosis and warrants further investigation.
Abuodeh
R O
RO
Valley Fever Center for Excellence, Veterans Affairs Medical Center, and University of Arizona, Tucson, Arizona, USA.
Shubitz
L F
LF
Siegel
E
E
Snyder
S
S
Peng
T
T
Orsborn
K I
KI
Brummer
E
E
Stevens
D A
DA
Galgiani
J N
JN
D000818:Animals; D000946:Antigens, Fungal / Q000276:immunology*; D003045:Coccidioides / Q000276:immunology*; D003047:Coccidioidomycosis / Q000517:prevention & control*; D005260:Female; D005656:Fungal Proteins; D005657:Fungal Vaccines / Q000276:immunology*; D006023:Glycoproteins / Q000276:immunology*; D007113:Immunity, Innate / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011392:Proline; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology*
D000946:Antigens, Fungal; D005656:Fungal Proteins; D005657:Fungal Vaccines; D006023:Glycoproteins; D007074:Immunoglobulin G; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; C102758:antigen 2, Coccidioides; D015847:Interleukin-4; D007371:Interferon-gamma; D011392:Proline