Mc. Grothaus et al., Selection of an immunogenic peptide mimic of the capsular polysaccharide of Neisseria meningitidis serogroup A using a peptide display library, VACCINE, 18(13), 2000, pp. 1253-1263
The presently available meningococcal vaccine is poorly immunogenic in infa
nts and fails to induce long-lasting immunity in adults. Efforts to convert
this TI-2 type vaccine into a T dependent vaccine ape being actively pursu
ed and include conjugate vaccine development. Alternatively, the meningococ
cal polysaccharide can be rendered into a T dependent antigen through the u
se of peptides which mimic the capsular polysaccharide complexed or conjuga
ted to potent protein carrier molecules. We have previously developed an an
ti-idiotypic monoclonal antibody (mAb) based peptide mimic of meningococcal
group C polysaccharide (MCPS). A direct approach to identification of pept
ide mimics of antigen is through the use of peptide display libraries. We h
ave utilized a phage library and a mAb with specificity for meningococcal g
roup A polysaccharide (MAPS) to screen for a peptide mimic of MAPS. Six dif
ferent peptide motifs were selected with the use of the mAb. Thirty-eight o
f the 60 sequenced phage clones were represented by motif 1 and 2 which dif
fered only in three amino acids at the carboxy terminus. Immunological assa
ys 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 proteos
omes resulted in an anti-MAPS antibody response. Priming with the peptide p
roteosome complex induced an anamnestic response indicating the formation o
f immunological memory. (C) 2000 Elsevier Science Ltd. All rights reserved.