RESUMEN
Sporotrichosis is an important zoonosis in Brazil and the most frequent subcutaneous mycosis in Latin America, caused by different Sporothrix species. Currently, there is no effective vaccine available to prevent this disease. In this study, the efficacy and toxicity of the adjuvant Montanide™ Pet Gel A (PGA) formulated with S. schenckii cell wall proteins (ssCWP) was evaluated and compared with that of aluminum hydroxide (AH). Balb/c mice received two subcutaneous doses (1st and 14th days) of either the unadjuvanted or adjuvanted vaccine candidates. On the 21st day, anti-ssCWP antibody levels (ELISA), the phagocytic index, as well as the ex vivo release of IFN-γ, IL-4, and IL-17 by splenocytes and IL-12 by peritoneal macrophages were assessed. Cytotoxicity of the vaccine formulations was evaluated in vitro and by histopathological analysis of the inoculation site. Both adjuvanted vaccine formulations increased anti-ssCWP IgG, IgG1, IgG2a, and IgG3 levels, although IgG2a levels were higher in response to PGA+CWP100, probably contributing to the increase in S. schenckii yeast phagocytosis by macrophages in the opsonophagocytosis assay when using serum from PGA+CWP100-immunized mice. Immunization with AH+CWP100 led to a mixed Th1/Th2/Th17 ex vivo cytokine release profile, while PGA+CWP100 stimulated a preferential Th1/Th2 profile. Moreover, PGA+CWP100 was less cytotoxic in vitro, caused less local toxicity and led to a similar reduction in fungal load in the liver and spleen of S. schenckii- or S. brasiliensis-challenged mice as compared with AH+CWP100. These results suggest that PGA may be an effective and safe adjuvant for a future sporotrichosis vaccine.
Asunto(s)
Adyuvantes Inmunológicos , Hidróxido de Aluminio/inmunología , Vacunas Fúngicas/efectos adversos , Vacunas Fúngicas/inmunología , Sporothrix/inmunología , Esporotricosis/prevención & control , Adyuvantes Inmunológicos/toxicidad , Hidróxido de Aluminio/toxicidad , Animales , Anticuerpos Antifúngicos/biosíntesis , Anticuerpos Antifúngicos/sangre , Anticuerpos Antifúngicos/inmunología , Brasil , Vacunas Fúngicas/administración & dosificación , Vacunas Fúngicas/química , Inmunidad Celular , Inmunogenicidad Vacunal , Interleucina-17/inmunología , Ratones , Ratones Endogámicos BALB C , Fagocitosis , Esporotricosis/inmunología , Balance Th1 - Th2 , VacunaciónRESUMEN
Two vaccines to treat phythiosis insidiosi in horses were evaluated in 71 Costa Rican horses between 1982 to 1988. One vaccine used a cell-mass (CMV) as antigen and the other a soluble concentrated antigen (SCAV). Both vaccines cured horses infected with Pythium insidiosum (p value approximately 14%). The age of lesions prior to vaccination was important in the response of the horses to immunotherapy. All horses with lesions 0.5 months or less in duration were cured regardless of the vaccine used. Horses with lesions two or more months old did not respond to either vaccine. The age of the horses did not have any influence on their response to the vaccinations. The CMV produced a prominent inflammatory reaction at the side of injection, while the SCAV gave a low inflammatory reaction. In addition, the CMV lost its effectiveness two to three weeks after its preparation. By contrast, the SCAV maintained its ability to cure horses even after 18 months. Immunotherapy using SCAV can thus be used as the vaccine of choice in early cases of equine cutaneous pythiosis insidiosi.