Experimental Viable Vaccine Against Pulmonary Coccidioidomycosis in Monkeys

Abstract

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.

Experimental Primary Cutaneous Coccidioidomycosis in the Monkey

“…As reported previously with strain Silveira (Converse et al, 1961), none of the strains used in this study exhibited any dissemination beyond the regional lymph nodes when used at the 10spore dose level; nor did strains D-76, Cash, or CW1 at the 100-spore dose level.…”

“…of systemic dissemination in approximately 18 proven cases of primary cutaneous infection (Wilson, Smith, and Plunkett, 1953;Guy and Jacob, 1926;Coccidioidomycosis Coop Study, 1961) have indicated the feasibility of such a vaccine. We reported (Converse, Castleberry, and Snyder, 1961) that the subcutaneous inoculation of Coccidioides immitis in the forearm of rhesus monkeys protected them from a later respiratory challenge with the same fungus. It was also shown that as few as ten arthrospores gave this protection without dissemination beyond the axillary lymph nodes, and that the protection was not strain-specific.…”

Experimental Irradiated Arthrospore Vaccine Against Coccidioidomycosis in Mice

“…Similar investigations have been made by Levine,Miller,and Smith (13) in the cynomologus monkey (Macaca iris), by Converse et al (4,5), Lowe et al (15), and Sinski et al (22) in the rhesus monkey (Macaca mulatta), and by Castleberry et al (1) in the dog.…”

“…Although surviving animals appear outwardly healthy, they retain the organism in the tissues in a viable state for long periods of time. Pappagianis et al (18,19) and Converse et al (3)(4)(5) have shown in both monkeys (M. iris and M. mulatta) and mice, and Castleberry et al (2) in dogs, that experimental viable C. immitis vaccines are far superior to nonviable vaccines in their protective effect against infection.…”

Coccidioidomycosis in Nonhuman Primates: Pathologic and Clinical Findings

“…Experimental infection of 93 rhesus macaques with Coccidioides was reported in 5 studies published between 1953 and 1966 (Table 3), using aerosolization, intratracheal injection, or natural exposure. 5,7,[16][17][18] The naturally exposed cases were infected by housing the animal in an area that was known to be infested. 18 When arthrospores were administered via intratracheal injection, all monkeys showed evidence of pulmonary infiltration.…”