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.
Grothaus
M C
MC
Department of Medicine and Pathology, Medical College of Ohio, Toledo 43699-0008, USA.
Srivastava
N
N
Smithson
S L
SL
Kieber-Emmons
T
T
Williams
D B
DB
Carlone
G M
GM
Westerink
M A
MA
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D000918:Antibody Specificity; D001428:Bacterial Vaccines / Q000276:immunology*; D001435:Bacteriophages / Q000235:genetics / Q000276:immunology; D001770:Blood Bactericidal Activity / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007117:Immunization, Secondary; D022401:Meningococcal Vaccines; D051379:Mice; D008807:Mice, Inbred BALB C; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D009345:Neisseria meningitidis / Q000145:classification / Q000276:immunology*; D019151:Peptide Library; D010455:Peptides / Q000008:administration & dosage / Q000138:chemical synthesis / Q000276:immunology* / Q000378:metabolism; D011135:Polysaccharides, Bacterial / Q000276:immunology*
D000911:Antibodies, Monoclonal; D001428:Bacterial Vaccines; D022401:Meningococcal Vaccines; D019151:Peptide Library; D010455:Peptides; D011135:Polysaccharides, Bacterial