Marta Feldmesser¹ and Arturo Casadevall^1,2

1Departments of Medicine (Division of Infectious Diseases) and Microbiology and Immunology², Albert Einstein College of Medicine, Golding Building Room 701, 1300 Morris Park Ave., Bronx, NY 10461

Received 1/5/98 Accepted 1/9/98

6. POLYCLONAL AB IN THERAPY AND ANIMAL STUDIES

Interest in the use of Ab therapy for cryptococcal disease predates the development of antifungal drugs. Prior to the development of mAb technology, heterologous serum was used. In 1925, Shapiro tried to both vaccinate a patient with cryptococcal meningitis and to infuse him intrathecally with rabbit serum from animals inoculated with the patient’s cryptococcal isolate. Therapy was discontinued because the patient became sensitized to the rabbit serum (73). Gordon and collaborators treated three patients with combined Amphotericin B and rabbit anticryptococcal Ab in the 1960s, with evidence for serologic response in at least one patient (74). In animal models, the effect of administration of polyclonal Ab preparations varied. Gadebusch showed protection of mice injected with rabbit anticryptococcal serum that was type specific (75). In another study, passive immunization by preincubation of yeast in polyclonal rabbit serum prolonged survival in complement sufficient, but not complement deficient mouse strains infected i.v. (76). Immune rabbit serum increased ingestion of cryptococci by rabbit peritoneal and alveolar macrophages in vitro and by murine neutrophils in vivo (77). However, when begun after infection, injection of rabbit or mouse plasma from animals immunized with cryptococci failed to protect mice infected with an ordinarily lethal inoculum (78). The differences in protection seen with Ab elicited by vaccination or passively administered polyclonal serum may have resulted from differences in epitope specificity or isotypic variances (see below), or from differences in route or timing of administration.