IDIOTYPE AND ANTI-ANTI-IDIOTYPE ANTIBODIES TO NEISSERIA-GONORRHOEAE LIPOOLIGOSACCHARIDES WITH BACTERICIDAL ACTIVITY BUT NO CROSS-REACTIVITYWITH RED-BLOOD-CELL ANTIGENS

A panel of murine mAb against three different epitopes of Neisseria go norrhoeae lipooligosaccharides (LOS) was developed. Only one of these, 3G5, displays bactericidal activity against all in vitro serum-resist ant strains of N. gonorrhoeae. Evidence suggests that sialylation, whi ch could occur in vivo, modifies some LOS epitopes in such a way that the strains become resistant to bactericidal activity and are no longe r recognized by specific antibodies. The epitope recognized by our bac tericidal mAb is not affected by sialylation as shown by immunoblot an alysis. We also provided evidence that the 3G5 epitope is different fr om RBC precursor Ag, since our mAb did not induce RBC agglutination. S ince LOS induce an immune response in a T cell-independent fashion and are highly toxic, they cannot be used for immunization. Use of anti-i diotypic antibodies (ald) could be a way to bypass these difficulties. Therefore, in the present study, ald were produced in rabbits and ren dered idiotype-specific by appropriate adsorption. These ald specifica lly bind to the relevant Id but not to LOS, and inhibit only the bindi ng of anti-LOS mAb (3G5) to LOS preparations from N. gonorrhoeae in a dose-response fashion. The specificity of our ald for the binding site of anti-LOS mAb is suggested by the binding inhibition of affinity-pu rified ald to Id by LOS. In addition, the capacity of ald to inhibit b actericidal activity of this anti-LOS mAb and the idiotypic cross-reac tivity between rat and mouse anti-LOS antibodies support this point. F inally, the elicitation of anti-LOS activity with bactericidal activit y upon immunization of naive mice with ald confirms the internal image properties of the ald. These data suggest that a bactericidal mAb sui table for immunoprotection was obtained, and the production of ald ope ns the door for development of a vaccine.