A STRATEGY FOR RATIONAL DESIGN OF FULLY SYNTHETIC GLYCOPEPTIDE CONJUGATE VACCINES

The present study describes a strategy to rationally design fully synt hetic glycopeptide conjugate vaccines, Glycopeptide immunogens were co nstructed by coupling synthetic oligosaccharides comprising repeating units of synthetic 3-beta-D-ribose-(l-l)-D-ribitol-5-phosphate (sPRP) to synthetic peptides containing potent T-helper cell determinants and B-cell epitopes of the Haemophilus influenzae type b (Hib) outer memb rane proteins (OMPs) P1, PZ, and P6, Rabbit immunogenicity studies rev ealed that some of these fully synthetic glycoconjugates were capable of eliciting high titers of both anti-PRP and anti-OMP immunoglobulin G antibodies, In addition, we systematically investigated the factors which could influence their immunogenicity. We observed that the magni tude of the anti-PRP antibody response markedly depended on the relati ve spatial orientation of sPRP and T-cell epitopes, the anti-PRP antib ody response was enhanced when a multiple antigenic peptide was used a s a carrier, the anti-PRP antibody response was optimal fur three PRP repeating units, and lipidation of peptide-PRP conjugates had a minima l effect on the magnitude of the anti-PRP antibody response, The resul ts of this study clearly demonstrate that coupling a carbohydrate hapt en to a peptide can provide T-cell help and convert it into a T-cell-d ependent antigen, The antisera raised against these conjugates were al so found to be protective against Hib infection in the infant rat mode l of bacteremia.