EPITOPE MAPPING OF THE 273-284 REGION OF HSV GLYCOPROTEIN-D BY SYNTHETIC BRANCHED POLYPEPTIDE CARRIER CONJUGATES

To investigate the antigenicity of a predicted epitope region of herpe s simplex virus gD, peptides comprising the 273-284 sequence have been synthesized and conjugated to a branched polypeptide with polylysine backbone (poly[L-Lys-(DL-Ala(m))], AK). In order to analyze the effect of the carrier on the solution conformation of the potential peptide- epitopes, three peptides (273-284, 273-281 and 276-284) and their poly peptide conjugates were studied by CD spectroscopy in PBS or in TFE. I n immunized BALB/c and CBA mice, the level of peptide-, conjugate- and carrier-specific antibody responses were measured. Conjugates with sy nthetic polypeptide carrier AK induced epitope-specific IgG responses, accompanied by the appearance of a low level of carrier-specific anti bodies. The cross-reactivity pattern of induced antibodies revealed th e presence of at least two functionally distinct, overlapping epitopes , the availability of which was influenced by flanking residues at the N-terminus. Preimmunization of BALB/c or CBA mice with the [276-284]- AK conjugate gate resulted in the production of HSV-specific antibodie s and in prolonged survival of animals infected with a lethal dose of herpes simplex virus. The degree of protection was comparable to that of [1-23]-AK conjugate (30).