DNA vaccination of mice to immunize against Coccidioides immitis

Life-long immunity follows most coccidioidal infections and vaccination with killed spherule vaccine protects mice from later infection. Indirect evidence implicates a proline-rich antigen (PRA) as a stimulus of cellular immunity. To study this directly, a 597 bp PCR amplimer encoding PRA was inserted into plasmid vectors VR1012 and VR1020 (Vical, San Diego CA). DNA sequencing verified orientation and reading frame. Female Swiss-Webster mice, 6-8 weeks old, received 100 μg i.m. of plasmid DNA. ELISA with recombinant PRA was used to detect a humoral response. After a single vaccination with either vector, PRA-specific IgG was detected by 2 wks (mean±SEM OD of 0.347±0.038 versus 0.128±0.004 for vector control mice, serum diluted 1:320, p<0.004). Antibodies were elevated for over 2 months. Vaccination repeated at 4 wks boosted IgG levels in 6 of 7 mice studied. In a preliminary study of intranasal C. immitis infection, 8 surviving mice had higher preinfection IgG levels in serum diluted 1:640 (0.939 ± 0.162) as compared to 4 mice who died before day 21 (0.494 ± 0.167). DNA vaccination will be a useful tool for studies of coccidioidal immunity.