The Influence of Branched Polypeptide Carriers on the Immunogenicity of Predicted Epitopes of HSV‐1 Glycoprotein D

HILBERT, F. HUDECZ, G. MEZÔ, I. MUCSI, J. KAJTÁR, I. KURUCZ, J. GERGELY, RAJNAVÖLGYI

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Abstract

To investigate the role of synthetic polypeptide carriers in inducing an epitope‐specific immune response relevant for vaccine design, peptides comprising two distinct regions of herpes simplex virus type I glycoprotein D (1–23 and 273–284) have been conjugated to the branched polypeptides with polylysine backbone, poly[L‐Lys‐(DL‐Alam)] (AK), or poly[L‐Lys‐(LeUi‐DL‐Alam)] (LAK) and to keyhole limpet haemocyanin (KLH). The magnitude, fine specificity and isotype distribution of the conjugate‐, peptide and carrier‐specific antibody responses were characterized in immunized BALB/c and CBA mice. Conjugates containing the polypeptide carrier AK were the most effective in inducing HSV gD‐peptide specific antibody responses while KLH peptide conjugates resulted in conjugate‐specific antibody responses without measurable peptide specificity. The efficacy of AK‐peptide conjugates was verified by the dominant appearance of peptide‐specific antibodies belonging to functionally efficient IgG isotopes, accompanied by low levels of carrier specific antibody responses. Preimmunization of BALB/ or CBA mice with AK conjugates comprising the 1–23 or 276–284 HSV peptides resulted in prolonged survival of animals infected with a lethal dose of infectious HSV‐1. The potency of these conjugates in eliciting a protective immune response shows a close correlation with the relative levels of conjugate‐induced virus specific antibodies and the neutralizing activity of sera as measured in preimmunized survivors.

Original languageEnglish
Pages (from-to)609-617
Number of pages9
JournalScandinavian Journal of Immunology
Volume40
Issue number6
DOIs
Publication statusPublished - Dec 1994

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ASJC Scopus subject areas

  • Immunology

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