CONJUGATES OF SYNTHETIC CYCLIC-PEPTIDES ELICIT BACTERICIDAL ANTIBODIES AGAINST A CONFORMATIONAL EPITOPE ON A CLASS-1 OUTER-MEMBRANE PROTEINOF NEISSERIA-MENINGITIDIS

Bactericidal antibodies directed against surface loops of class 1 oute r membrane proteins play a crucial role in protection against meningit is and sepsis caused by Neisseria meningitidis, So far, all efforts to obtain protective antibodies against these apparently conformational epitopes by using linear peptide analogs have been in vain. In this st udy, conjugates of head-to-tail cyclic peptides encompassing the predi cted top of a protective surface loop were used for immunization. A se ries of 18 cyclic peptides with a ring size ranging from 7 to 17 resid ues, conjugated to tetanus toroid, nas investigated. Antipeptide and a nti-whole-cell immunoglobulin G (IgG) titers elicited by the conjugate s were determined. Conjugates of three peptides, containing 14, 15, an d 17 amino acid residues (peptides 7, 12, and 13, respectively), induc ed an anti-whole-cell Liter when Quillaja saponin A was used as the ad juvant. When alum was used as the adjuvant, the conjugate of peptide 1 2 did not elicit an anti-whole-cell response, From the Quillaja saponi n A group, some of the sera obtained with conjugates of peptides 7 and 12 and all sera obtained with the peptide 13 conjugate were bacterici dal in vitro. None of the sera evoked,vith alum as the adjuvant showed bactericidal activity. Nonbactericidal sera contained IgG1 primarily, whereas bactericidal sera showed significant titers of IgG2a and IgG2 b. Class 1 protein-derived synthetic cyclic peptides which are capable of eliciting bactericidal antibodies, such as peptide 13 derived from meningococcal strain H44/76, represent potential candidates for a (se mi)synthetic vaccine against meningococcal disease.