Toward developing a universal treatment for fungal disease using radioimmunotherapy targeting common fungal antigens.

BACKGROUND: Previously, we demonstrated the ability of radiolabeled antibodies recognizing the cryptococcal polysaccharide capsule to kill Cryptococcus neoformans both in vitro and in infected mice. This approach, known as radioimmunotherapy (RIT), uses the exquisite ability of antibodies to bind antigens to deliver microbicidal radiation. To create RIT reagents which would be efficacious against all major medically important fungi, we have selected monoclonal antibodies (mAbs) to common surface fungal antigens such as heat shock protein 60 (HSP60), which is found on the surface of diverse fungi; beta (1,3)-glucan, which is a major constituent of fungal cell walls; ceramide which is found at the cell surface, and melanin, a polymer present in the fungal cell wall. METHODS: MAbs 4E12, an IgG2a to fungal HSP60; 2G8, an IgG2b to beta-(1,3)-glucan; and 6D2, an IgM to melanin, were labeled with the alpha particle emitting radionuclide 213-Bismuth ((213)Bi) using the chelator CHXA". B11, an IgM antibody to glucosylceramide, was labeled with the beta emitter 188-Rhenium ((188)Re). Model organisms Cryptococcus neoformans and Candida albicans were used to assess the cytotoxicity of these compounds after exposure to either radiolabeled mAbs or controls. RESULTS: (213)Bi-mAbs to HSP60 and to the beta-(1,3)-glucan each reduced the viability of both fungi by 80-100%. The (213)Bi-6D2 mAb to melanin killed 22% of C. neoformans, but did not kill C. albicans. B11 mAb against fungal ceramide was effective against wild-type C. neoformans, but was unable to kill a mutant lacking the ceramide target. Unlabeled mAbs and radiolabeled irrelevant control mAbs caused no killing. CONCLUSION: Our results suggest that it is feasible to develop RIT against fungal pathogens by targeting common antigens and such an approach could be developed against fungal diseases for which existing therapy is unsatisfactory.

[Ecological aspects of American cutaneous leishmaniasis. 9. Prevalence/incidence of the human infection in the municipality of Pedro de Toledo and Miracatu, São Paulo, Brazil]. / Aspectos ecológicos da leishmaniose tegumentar americana 9. Prevalência/incidência da infecção humana nos municípios de Pedro de Toledo e Miracatu, São Paulo, Brasil.

The epidemiologic study was conducted during the 1973-1984 period. The clinical prospective exam and Montenegro skin, immunofluorescent and passive hemagglutination tests have been carried out in three small localities between Pedro de Toledo e Miracatu municipalities, São Paulo, Brazil. The retrospective study of human-cases involved 108 and 65 cases registered in Pedro de Toledo e Miracatu, respectively. In the three communities studied, 273 people were examined clinically and serologically. Twenty two individuals had had signals of cutaneous leishmaniasis; 10.2 and 12.8% were seropositive to IF and HA. Leishmanin skin testing of a sample of 154 people residents in Pedra do Largo showed prevalence of Leishmania infection in 25.5%. This result involved individual of all ages and sex. However, 5.8% of them were from 0 to 9 years old. The data confirmed that active parasite transmission didn't occur every year, either. The human infection seems not to depend on man contact with a forest. The incidence relatively low suggests low endemic area for cutaneous leishmaniasis and an explosive behavior of the cases. The temporal distribution of disease was irregular and the epidemiological pattern seen was different from the other endemic area of South America.