Immunization of mice against coccidioidomycosis. J. Bacteriol. 84:46-52. 1962-The observed lower virulence of Coccidioides immitis arthrospores of the M-11 strain compared with the Cash strain was ascribed to the lower ability of the M-11 spores to invade the lungs and brain. Endospores of strain M-11, grown in synthetic medium, were equally as virulent by the intraperitoneal route as arthrospores of strain Cash. Immunization of mice with viable strain M-11 arthrospores protected approximately 50 % of the animals against challenge with strain Cash arthrospores. This was evidenced by lower mortality over a 5-month period and lack of gross pathological lesions in killed animals. Although fewer lesions resulted after the use of a viable vaccine, higher survival was obtained with formaldehyde-killed arthrospores. Either preparation tended to confine the infection to the peritoneal cavity.

No abstract

coccidioidomycosis was studied in the monkey (Macaca mulatta) to find a suitalle strtain of Coccidioides immitis for use as a viable vaccine. Intradermal inoculation (medial surface of the right forearm) produced more severe vtaccination reactions (draining vaccination site and axillary lymph node hypertrophy) than did subcutaneous injection. A subcutaneous vaccine dose of 10 arthrospores resulted in less reaction t han a 100-spore dose. Moreover, dissemination b)eyond the regional lymph nodes did not occur after injection of ten spores of even the most virulent strains of C. immitis. Two of the five strains tested (Silveira, M-11, D-76, Cash, and a colonial isolate from Cash designated CW1) exhibited very mild vaccination reactions and appeared to have been cleared from the tissues upon necropsy at 10 months postvaccination. These two strains (Cash and CW1) appear promising for further immunological studies with a viable vaccine.

Macaca mulatta) vaccinated by subcutaneous injection in the forearm with from 10 to 108 viable Coccidioides immitis arthrospores were protected against respiratory challenge with approximately 7000 viable arthrospores administered 6 months after vaccination. Protection was evident from: the healthy appearance throughout 4 months after respiratory challenge; negative chest X rays at 15, 30, 60, and 120 days; and only very minor histopathological pulmonary changes on autopsy at 120 days, with negative lung cultures in 80% of the animals. This was in striking contrast to the outward clinical appearance of control monkeys that were unvaccinated or had received nonviable arthrospore vaccines. These monkeys showed severe disease (loss of weight, accelerated respiration, severe coughing, general debilitation), positive X rays, massive pulmonary destruction, positive lung cultures, and death of five of nine animals. The appearance of spherules (very few in number, accompanied by very minor pathological changes) in the lungs of some of the "dissemination controls" (subcutaneous viable vaccination without respiratory challenge) indicated possible dissemination from the primary cutaneous infection, although oral transmission from the cutaneous lesions could not be ruled out.

Control of tissue reactions in monkeys vaccinated with viable Coccidioides immitis by prevaccination with killed Coccidioides immitis. J. Bacteriol. 90:783-788. 1965.-Control of undesirable tissue reactions resulting from the subcutaneous injection of 150 viable arthrospores of Coccidioides immitis (strain D-76) was obtained by four injections of formalin-killed arthrospores 14, 12, 8, and 4 weeks (total dose, 36 mg) before injection of the viable arthrospores. Only 6 and 12% of these vaccinated animals exhibited ulceration and lymphadenopathy, respectively, as compared with 100 and 83% of the animals receiving only the viable vaccine. Agar-gel immunodiffusion precipitin titers of approximately 1:64 were evident 3 months after vaccination in animals receiving both vaccines, as compared with 1:128 in those injected with the viable vaccine alone. The above data indicated that somatic reactions to injection of a viable vaccine could be eliminated by preinjection of a killed vaccine. However, 6 months after vaccination, respiratory challenge (7,500 strain Cash arthrospores) indicated that this treatment also impaired the protective effect of the viable vaccine. All animals receiving both vaccines developed mild pulmonary coccidioidomycosis, whereas only 50% of the animals receiving only the viable vaccine were infected. In addition, the group receiving both vaccines demonstrated a more rapid and higher postchallenge precipitin titer. All vaccinated animals (those receiving the killed, the viable, or a combination of the two vaccines) survived for 4 months after challenge, as compared with 88% mortality (50% within 14 days) in the nonvaccinated controls.