Two different methods result in the selection of peptides that induce a protective antibody response to Neisseria meningitidis serogroup C.

ABSTRACT

Neisseria meningitidis is a leading cause of morbidity and mortality worldwide. The presently available capsular polysaccharide vaccine is poorly immunogenic in children under the age of 2 due to its T-independent (TI) nature. Efforts to overcome the TI response elicited by the polysaccharide vaccine have led to the development of polysaccharide-protein conjugate vaccines. Although a T-dependent (TD) response can be achieved in young children, the response to the polysaccharide still retains characteristics of a TI antibody response. An alternative method of potentially inducing a TD response to a carbohydrate antigen is through peptides that mimic the capsular polysaccharide. Our laboratory, through the production of an anti-idiotypic (anti-id) monoclonal antibody, designated 6F9, has previously identified a peptide mimic of the meningococcal serogroup C polysaccharide (MCPS). Using the same selecting monoclonal antibody (mAb), 1E4, we have screened a phage display library and identified 13 unique peptides that bound specifically to mAb1E4. Two peptides, Pep1C and Pep2C, that demonstrated the highest binding to mAb1E4, were selected, complexed to proteosomes, and used to immunize Balb/c mice. Of the 13 peptide motifs, only one peptide motif, that of Pep2C, was found to resemble the immunogenic peptide sequence of the anti-id selected with the same mAb, although many contained several similar amino acid residues. Immunization with Pep2C, but not Pep1C, induced a significant and functional anti-MCPS antibody response that conferred protection from a lethal challenge with meningococci. Our results indicate that immunization with a peptide of N. meningitidis serogroup C, screened with the same mAb that selected an anti-id of MCPS, induces a functional and protective anti-MCPS immune response similar to that of the anti-id. This study demonstrates that two different selection methods, production of an anti-id and biopanning using a phage display library, can be used to select functional and protective peptides of MCPS with similar moieties.