IMMUNIZATION WITH ANTIBODIES THAT MIMIC LPS PROTECTS AGAINST GRAM-NEGATIVE BACTERIAL SEPSIS

We developed 9H1.B11, an anti-idiotypic anti-deep core/lipid A (DCLA), murine monoclonal antibody (mAb) that mimics the conserved DCLA regio n of lipopolysaccharide (LPS). It recognizes an epitope in the variabl e region of an DCLA mAb, binds to the murine macrophage cell surface, and inhibits LPS-induced macrophage cytokine secretion. We hypothesize d that (1) active immunization with mAb 9H1.B11 would be associated wi th the development of anti-DCLA antibodies and (2) immunization would protect against subsequent gram negative bacterial challenge. Mice wer e immunized for 8 weeks before intraperitoneal (ip) challenge with Esc herichia coil O111:B4 bacteria. Control animals were immunized with an irrelevant IgM antibody 8133 (negative control) or with LPS derived f rom Salmonella minnesota Re bacteria (positive control). Sera from imm unized mice were collected, and titers against the core region of LPS (Re) and against LPS derived from the infecting E. coli strain were de termined. Mice immunized with mAb 9H1.B11 developed measurable titers against S. minnesota Re LPS but not against the challenge strain of E. coil. However, immunization with 9H1.B11 on S. minnesota Re LPS prote cted against subsequent infection due to E. coli O111:B4 (100% surviva l). The group of mice immunized with IgM 8133 exhibited only 25% survi val. The development of an anti-S. minnesota Re LPS titer after immuni zation with 9H1.B11 provides further evidence that a portion of 9H1.B1 1 mimics the conserved DCLA region of LPS. We believe that this approa ch holds considerable promise and plan further studies to define the m echanism by which protective capacity occurs. (C) 1997 Academic Press.