Selection of an immunogenic peptide mimic of the capsular polysaccharide of Neisseria meningitidis serogroup A using a peptide display library

The presently available meningococcal vaccine is poorly immunogenic in infants and fails to induce long-lasting immunity in adults. Efforts to convert this TI-2 type vaccine into a T dependent vaccine are being actively pursued and include conjugate vaccine development. Alternatively, the meningococcal polysaccharide can be rendered into a T dependent antigen through the use of peptides which mimic the capsular polysaccharide complexed or conjugated to potent protein carrier molecules. We have previously developed an anti-idiotypic monoclonal antibody (mAb) based peptide mimic of meningococcal group C polysaccharide (MCPS). A direct approach to identification of peptide mimics of antigen is through the use of peptide display libraries. We have utilized a phage library and a mAb with specificity for meningococcal group A polysaccharide (MAPS) to screen for a peptide mimic of MAPS. Six different peptide motifs were selected with the use of the mAb. Thirty-eight of the 60 sequenced phage clones were represented by motif 1 and 2 which differed only in three amino acids at the carboxy terminus. Immunological assays were performed. Phage clones with motif 1 and 2 were capable of binding human hyperimmune sera and inhibiting the binding of human hyperimmune sera to nominal antigen. Immunization with motif 1 peptide complexed to proteosomes resulted in an anti-MAPS antibody response. Priming with the peptide proteosome complex induced an anamnestic response indicating the formation of immunological memory.