MOLECULAR ADJUVANT EFFECTS OF A CONFORMATIONALLY BIASED AGONIST ELF HUMAN C5A ANAPHYLATOXIN

A conformationally biased decapeptide agonist of human C5a anaphylatox in (YSFKPMPLaR) was used as a molecular adjuvant in stimulating Ab res ponses against peptide epitopes derived from human MUC1 glycoprotein a nd the human mu and kappa opioid receptors. C57BL6 mice were immunized with the MUC1 epitope (YKQGGFLGL); the C5a agonist (YSFKPMPLaR); YSFK PMPLaR and YKQGGFLGL together, but unconjugated; a C5a-active, MUC1 ep itope construct (YKQGGFLGLYSFKPMPLaR); and a C5a-inactive, reversed mo iety construct (YSFKPMPLaRYKQGGFLGL). High Ab titers specific for the MUC1 epitope were observed Only in mice immunized with the C5a-active epitope construct. Similar results were obtained in BALB/c mice immuni zed with the C5a-active, MUC1 epitope construct, Abs from the sera of the C57BL6 mice were predominately of the IgG2a, IgC2b, and IgM isotyp es and were reactive against human recombinant MUC1 and MUC1 expressed by the Panc-1 M1F.15 pancreatic cell line, When compared with the cor responding KLH-epitope conjugates in C57BL6 mice, the epitope-C5a agon ist constructs produced titers of specific IgG Abs of isotypes distinc t from those generated by the keyhole limpet hemocyanin-epitope conjug ates, Rabbits immunized with a mu opioid receptor epitope-C5a agonist construct (GDLSDPCGNRTNLGGRDSLYSFKPMPLaR) or a kappa opioid receptor e pitope-C5a agonist construct (FPGWAEPDSNGSEDAQLYSFKPMPLaR) generated h igh titer, epitope-specific Ab responses, Ab titers generated in respo nse to the opioid epitope-C5a agonist constructs were comparable to th ose generated by the opioid KLH-epitope conjugates, The results of thi s study are discussed in terms of possible mechanisms by which the con formationally biased C5a agonist serves as a molecular adjuvant.