Proteins and their derived peptides as carriers in a conjugate vaccine for Streptococcus pneumoniae: self-heat shock protein 60 and tetanus toxoid.
We induced T cell help for vaccination against Streptococcus pneumoniae (Pn) using self and foreign peptides and their source proteins conjugated to the capsular polysaccharide (CPS) of type 4 Pn; the carriers were self-heat shock protein 60 (HSP60) and tetanus toxoid (TT). We measured the production of IgG Abs to the CPS and the carriers, and tested resistance to challenge with highly lethal amounts of Pn injected i.p. (LD(50) x 10(3)-10(6)). We now report that vaccination protects old and young mice from bacterial challenge; however, there were significant differences in vaccine efficacy based on the carrier. Self-HSP60 peptide p458m was more effective than the whole HSP60 molecule and was equally effective compared with TT. Both p458m and TT were more protective than the TT-derived peptide p30 after a single vaccination. However, peptide p30 was effective in more MHC genotypes than was p458m. Unlike other vaccines, protection conferred by p458m was not related to the amount of anti-CPS Ab: mice that produced very little Ab were still protected from highly lethal doses of bacteria (LD(50) x 10(5)-10(6)). Furthermore, unlike the other carriers, there was no Ab response to the p458m carrier. Thus, peptides, self as well as foreign, can provide T cell help that differs functionally from that provided by the whole parent protein.
Amir-Kroll
Hila
H
Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
Nussbaum
Gabriel
G
Cohen
Irun R
IR
D000367:Age Factors; D000595:Amino Acid Sequence; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D001324:Autoantigens / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D002352:Carrier Proteins / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use; D018834:Chaperonin 60 / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D007115:Immunization Schedule; D007074:Immunoglobulin G / Q000096:biosynthesis; D007279:Injections, Subcutaneous; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use; D011008:Pneumococcal Infections / Q000276:immunology / Q000517:prevention & control; D022242:Pneumococcal Vaccines / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use; D011135:Polysaccharides, Bacterial / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D013045:Species Specificity; D013745:Tetanus Toxoid / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use
D001323:Autoantibodies; D001324:Autoantigens; D002352:Carrier Proteins; D018834:Chaperonin 60; D007074:Immunoglobulin G; D010446:Peptide Fragments; D022242:Pneumococcal Vaccines; D011135:Polysaccharides, Bacterial; D013745:Tetanus Toxoid; D018074:Vaccines, Conjugate; C053136:pneumonococcal polysaccharide, type 4