ISOTYPE SWITCHING FROM IGG3 TO IGG1 CONVERTS A NONPROTECTIVE MURINE ANTIBODY TO CRYPTOCOCCUS-NEOFORMANS INTO A PROTECTIVE ANTIBODY

Passively administered mAbs to Cryptococcus neoformans capsular polysa ccharide can alter the course of infection in mouse models. In prelimi nary studies of passive Ab efficacy, most IgM, IgA, and IgG1 mAbs were protective, but the few IgG3 mAbs tested did not confer significant p rotection. Because IgG3 is effective in pneumococcal infections, this phenomenon was examined more rigorously by generating an IgG1 switch v ariant from the nonprotective IgG3 mAb 3E5 and comparing its protectiv e efficacy in a murine model of i.v. infection by using strains of bot h the A and D serotypes. The 3E5 IgG3 mAb did not prolong survival or reduce organ fungal burden. Rather, the IgG3 decreased survival relati ve to controls. In contrast, the IgG1 switch variant of 3E5 significan tly prolonged survival, reduced organ colony-forming units, and reduce d serum polysaccharide Ag level in infected mice. The results establis h that isotype is important for Ab efficacy against C. neoformans.