Safety, Antigenicity, and Efficacy of a Recombinant Coccidioidomycosis Vaccine in Cynomolgus Macaques (Macaca fascicularis) SUZANNE M. JOHNSON, a NICHOLAS W. LERCHE, b DEMOSTHENES PAPPAGIANIS, a JOANN L. YEE, b JOHN N. GALGIANI, c AND RICHARD F. HECTOR d a Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, California 95616, USA b California National Primate Research Center, University of California, Davis, California 95616, USA c Valley Fever Center for Excellence, University of Arizona and Southern Arizona, VA Health Care System, Tucson, Arizona 85723, USA d Institute for Global Health, University of California, San Francisco 94105, California, USA ABSTRACT: 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. Address for correspondence: Nicholas W. Lerche, D.V.M. M.P.V.M., California National Primate Research Center, University of California, Davis, CA 95616. Voice: 530-752-6490; fax: 530-752- 4816. nwlerche@ucdavis.edu Ann. N.Y. Acad. Sci. 1111: 290–300 (2007). C  2007 New York Academy of Sciences. doi: 10.1196/annals.1406.042 290