Safety, antigenicity, and efficacy of a recombinant coccidioidomycosis vaccine in cynomolgus macaques (Macaca fascicularis).

The safety, immunogenicity and efficacy of recombinant Ag2/PRA106 + CSA chimeric fusion protein (CFP) vaccine in ISS/Montanide adjuvant-administered intramuscular (IM) was assessed in adult female cynomolgus macaques challenged with Coccidioides posadasii. Animals received three immunizations with either 5 � g CFP, 50-� g CFP, or adjuvant alone and were challenged 4 weeks following the final immunization. Although significant antibody response was pro- duced in response to vaccination, there were no discernable adverse ef- fects, suggesting that the vaccine was well tolerated. Upon intratracheal challenge, all animals showed evidence of disease. Two animals that re- ceived 5-� g doses of CFP were euthanatized prior to the study's end be- cause of severe symptoms. Animals vaccinated with 50-� g doses of CFP showed evidence of enhanced sensitization compared to adjuvant controls and animals vaccinated with 5-� g doses of CFP. This was based on higher serum anti-CFP titers, enhanced secretion of interferon-gamma (IFN-� ) from stimulated bronchoalveolar lavage mononuclear cells (BALMC), re- duced pulmonary radiologic findings following intratracheal challenge, reduced terminal complement fixation titers, and reduced necropsy find- ings. Overall the vaccine was well tolerated, induced sensitization, and resulted in a protective response when given at the higher 50-� g dose.