Complement and Fc function are required for optimal antibody prophylaxis against Pneumocystis carinii pneumonia

Pneumocystis carinii is an opportunistic fungal pathogen that causes P. carinii pneumonia (PCP) in the immunocompromised host. We investigated the role of antibody Fe-mediated function in passive prophylaxis against the development of PCP in SCID mice. By comparison of anti-mouse P. carinii immunoglobulin G1 monoclonal antibody (MAb) 4F11(G1) and its F(ab')2 derivative in an intranasal immunoprophylaxis model, we determined that Fc-mediated function is required for maximum effect of this antibody. Comparison of efficacy of antibody prophylaxis in SCID mice depleted of complement to that in nondepleted mice demonstrated that complement fixation by MAb 4F11(G1) is also necessary for optimal effect of passively administered antibody, although residual protection was observed in complement-depleted SCID mice. The necessity of complement for optimal PCP prophylaxis by MAb 4F11(G1) suggests that complement may play a role in antibody-mediated protection against development of PCP.