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, 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.
Hilbert
A
A
Department of Immunology, L. Eötvös University, Göd, Hungary.
Hudecz
F
F
Mezô
G
G
Mucsi
I
I
Kajtár
J
J
Kurucz
I
I
Gergely
J
J
Rajnavölgyi
E
E
D000595:Amino Acid Sequence; D000818:Animals; D000956:Antigens, Viral / Q000008:administration & dosage / Q000276:immunology*; D004337:Drug Carriers / Q000737:chemistry; D000939:Epitopes / Q000276:immunology; D018259:Herpesvirus 1, Human / Q000276:immunology*; D007132:Immunoglobulin Isotypes; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010455:Peptides / Q000737:chemistry / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000008:administration & dosage / Q000276:immunology*; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology
D000956:Antigens, Viral; D004337:Drug Carriers; D000939:Epitopes; D007132:Immunoglobulin Isotypes; D010455:Peptides; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C039447:glycoprotein D, Human herpesvirus 1