Idiotype and anti-anti-idiotype antibodies to Neisseria gonorrhoeae lipooligosaccharides with bactericidal activity but no cross-reactivity with red blood cell antigens.

Abstract

A panel of murine mAb against three different epitopes of Neisseria gonorrhoeae lipooligosaccharides (LOS) was developed. Only one of these, 3G5, displays bactericidal activity against all in vitro serum-resistant strains of N. gonorrhoeae. Evidence suggests that sialylation, which could occur in vivo, modifies some LOS epitopes in such a way that the strains become resistant to bactericidal activity and are no longer recognized by specific antibodies. The epitope recognized by our bactericidal mAb is not affected by sialylation as shown by immunoblot analysis. We also provided evidence that the 3G5 epitope is different from RBC precursor Ag, since our mAb did not induce RBC agglutination. Since LOS induce an immune response in a T cell-independent fashion and are highly toxic, they cannot be used for immunization. Use of anti-idiotypic antibodies (aId) could be a way to bypass these difficulties. Therefore, in the present study, aId were produced in rabbits and rendered idiotype-specific by appropriate adsorption. These aId specifically bind to the relevant Id but not to LOS, and inhibit only the binding of anti-LOS mAb (3G5) to LOS preparations from N. gonorrhoeae in a dose-response fashion. The specificity of our aId for the binding site of anti-LOS mAb is suggested by the binding inhibition of affinity-purified aId to Id by LOS. In addition, the capacity of aId to inhibit bactericidal activity of this anti-LOS mAb and the idiotypic cross-reactivity between rat and mouse anti-LOS antibodies support this point. Finally, the elicitation of anti-LOS activity with bactericidal activity upon immunization of naive mice with aId confirms the internal image properties of the aId. These data suggest that a bactericidal mAb suitable for immunoprotection was obtained, and the production of aId opens the door for development of a vaccine.