Ro. Abuodeh et al., Resistance to Coccidioides immitis in mice after immunization with recombinant protein or a DNA vaccine of a proline-rich antigen, INFEC IMMUN, 67(6), 1999, pp. 2935-2940
Two inbred strains of mice (BALB/e 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 signific
ant weight loss, and quantitative CFUs in the lungs ranged from 5.9 to 6.4
log(10). In contrast, groups of mice immunized with either rPRA or DNA vacc
ine had significantly smaller pulmonary fungal burdens, ranging from 3.0 to
4.5 log(10) fewer CFUs, In vitro immunologic markers of lymphocyte prolife
ration and gamma interferon (IFN-gamma) release after splenocytes were stim
ulated with rPRA correlated with protection. Also, plasma concentrations of
rPRA-specific total immunoglobulin G (IgG), IgG1, and IgG2a showed increas
es in vaccinated mice. These studies expand earlier work by demonstrating p
rotection in mice which differ in H-2 background, by using an adjuvant that
is potentially applicable to human use, and by achieving comparable protec
tions with a DNA-based vaccine. Our in vitro results substantiate a Th1 res
ponse as evidenced by IFN-gamma release and increased IgG2a, However, IgG1
was also stimulated, suggesting some Th2 response as well. PRA is a promisi
ng vaccine candidate for prevention of coccidioidomycosis and warrants furt
her investigation.