Enhancement of Immune Responses in Mice by a Booster Injection of Coccidioides Spherules

Abstract

Induced immunity to Coccidioides immitis in mice challenged intranasally was enhanced greatly by the injection of a booster dose of 20 to 200 µg of killed spherules; fungal multiplication was suppressed up to 5 million-fold and 60 to 75% of boosted mice harbored no organisms in their lungs at 10 to 90 days postchallenge with arthrospore doses as high as 100 LD50. Enhancement of immunity was most pronounced when the booster injection was given at >2 months postvaccination and 6 to 7 days before challenge and was not induced by injecting another fungus, Cryptococcus neoformans.Low numbers of C. immitis in the lungs of boosted mice reflected marked clearance activity during the first 3 days postchallenge. In contrast, clearance activity during this period was less in nonboosted mice and was observed only in those vaccinated <2 months before challenge. Additionally, enhanced clearance in the lungs of boosted mice was paralleled by an early rise in numbers of inflammatory cells obtained by tracheobronchial wash; total cell numbers reached a maximum 2 to 3 days earlier in boosted than in nonboosted mice.Despite the demonstration of precipitins, attempts to transfer immunity passively with serum were unsuccessful. However, less fungal multiplication occurred after challenge in nonvaccinated recipients of live splenic cells from boosted mice than in recipients of live cells from normal mice or killed cells from boosted mice. The role of cells or serum in immunity was difficult to assess in passive transfer studies, because injection of normal splenic cells, their carrier fluid, or normal serum into intranasally infected mice often potentiated their infection.