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 Fc-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.
Wells
Jesse
J
University of Rochester School of Medicine and Dentistry, Department of Pediatrics, Box 690, 601 Elmwood Avenue, Rochester, NY 14642, USA.
Haidaris
Constantine G
CG
Wright
Terry W
TW
Gigliotti
Francis
F
D000818:Animals; D000908:Antibodies, Fungal / Q000008:administration & dosage*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D003165:Complement System Proteins / Q000172:deficiency / Q000502:physiology*; D007141:Immunoglobulin Fc Fragments / Q000502:physiology*; D051379:Mice; D016513:Mice, SCID; D045363:Pneumocystis carinii / Q000276:immunology*; D011020:Pneumonia, Pneumocystis / Q000276:immunology* / Q000517:prevention & control*
D000908:Antibodies, Fungal; D000911:Antibodies, Monoclonal; D007141:Immunoglobulin Fc Fragments; D003165:Complement System Proteins