THE INFLUENCE OF BRANCHED POLYPEPTIDE CARRIERS ON THE IMMUNOGENICITY OF PREDICTED EPITOPES OF HSV-1 GLYCOPROTEIN-D

To investigate the role of synthetic polypeptide carriers in inducing an epitope-specific immune response relevant for vaccine design, pepti des comprising two distinct regions of herpes simplex virus type I gly coprotein D (1-23 and 273-284) have been conjugated to the branched po lypeptides with polylysine backbone, poly[L-Lys-(DL-Ala(m))] (AK), or poly[L-Lys-(Leu(i)-DL-Ala(m))] (LAK) and to keyhole limpet haemocyanin (KLH). The magnitude, fine specificity and isotype distribution of th e conjugate-, peptide- and carrer-specific antibody responses were cha racterized in immunized BALB/c and CBA mice. Conjugates containing the polypeptide carrier AK were the most effective in inducing HSV gD-pep tide-specific antibody responses while KLH peptide conjugates resulted in conjugate-specific antibody responses without measurable peptide s pecificity. The efficacy of AK-peptide conjugates was verified by the dominant appearance of peptide-specific antibodies belonging to functi onally efficient IgG isotopes, accompanied by low levels of carrier sp ecific antibody responses. Preimmunization of BALB/ or CBA mice with A K conjugates comprising the 1-23 or 276-284 HSV peptides resulted in p rolonged survival of animals infected with a lethal dose of infectious HSV-1. The potency of these conjugates in eliciting a protective immu ne response shows a close correlation with the relative levels of conj ugate-induced virus-specific antibodies and the neutralizing activity of sera as measured in preimmunized survivors.