Coccidioides immitis vaccine: potential of an alkali-soluble, water-soluble cell wall antigen.

C-ASWS-M, the alkali-soluble, water-soluble cell wall antigen of Coccidioides immitis mycelia, was evaluated for its vaccine potential in mice. Vaccination with 0.5-, 1.5-, or 3-mg doses of C-ASWS-M in complete Freund adjuvant provided a significant level of protection against intraperitoneal challenge with 1,500 arthroconidia (P < 0.0001 with each dose). Vaccination with 1 mg of C-ASWS-M protected mice against intranasal challenge with 50 (P < 0.05) and 500 (P < 0.01) arthroconidia, but not against intranasal challenge with 1,500 arthroconidia (P > 0.05).

In vitro lymphocyte responses of coccidioidin skin test-positive and -negative persons to coccidioidin, spherulin, and a coccidioides cell wall antigen.

The biological activity of C-ASWS, an alkali-soluble, water-soluble cell wall antigen isolated from mycelial-phase cells of Coccidioides immitis, was compared with that of a commercial coccidioidin (CDN; Cutter Laboratories); CDN-TS, a toluene-induced lysate of mycelial-phase cells; and spherulin, a spherule-derived extract of C. immitis. Lymphocytes obtained from healthy CDN skin test-positive donors (group I), healthy skin test-negative donors (group II), and patients with active coccidioidomycosis (group III) were assayed for lymphocyte transformation and production of macrophage inhibitory factor in response to the Coccidioides antigens. C-ASWS, CDN CDN-TS, and spherulin were each effective in eliciting blastogenic responses in lymphocytes of group I subjects. However, only C-ASWS and CDN-TS were effective in eliciting macrophage inhibitory factor production. The responses of group III subjects (patients) were depressed and, in most instances, were indistinguishable from those obtained in lymphocytes of group II subjects.

In vivo and in vitro cell-mediated responses in coccidioidomycosis. I. Immumologic responses of persons with primary, asymptomatic infections.

Chest roentgenograms of 58 children who were skin test positive to coccidioidin and resided in an area endemic for coccidioidomycosis revealed that 34 per cent had roentgenographic evidence of an inflammatory process, 14 per cent showed calcific densities, and 52 per cent showed no evidence of infection. The in vitro lymphocyte responses of children who had evidence of an inflammatory process (Group I) were compared with those of children who had calcific densities (Group II); those of children who were coccidioidin skin test negative and had normal chest roentgenograms (Group III); and those of patients who had active coccidioidomycosis (Group IV). The mean lymphocyte transformation responses (expressed as cpm times 10-(4)) of Groups I, II, III, and IV to a coccidioides antigen were 16.8, 19.5, 4.2, and 7.0, respectively. The mean migration inhibitory factor responses of these groups were 22.4, 20.0, 1.2, and 4.0 per cent, respectively. Thus, the over-all responses of children in Groups I and II were comparable to each other, whereas the responses of patients in Group IV were depressed to the extent that they were indistinguishable from those of coccidioidin skin test-negative donors in Group III. Follow-up chest roentgenograms taken 3 months after the immunologic assays were performed revealed that the one subject in Group I who had been nonresponsive in the lymphocyte assays had now stabilized his infection, as evidenced by calcifications. In contrast, the 2 subjects in Group I who had yet to stabilize their infection had exhibited strong in vitro lymphocyte responses. These findings suggest that primary, asymptomatic coccidioidomycosis is not associated with an immunologically nonresponsive state. However, patients with active, progressive coccidioidomycosis do have a depressed immunologic response to coccidioides antigens.