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

被引:19
作者
HILBERT, A
HUDECZ, F
MEZO, G
MUCSI, I
KAJTAR, J
KURUCZ, I
RAJNAVOLGYI, E
GERGELY, J
机构
[1] EOTVOS LORAND UNIV, DEPT IMMUNOL, H-2131 GODOLLO, HUNGARY
[2] HUNGARIAN ACAD SCI, PEPTIDE CHEM RES GRP, BUDAPEST, HUNGARY
[3] ALBERT SZENT GYORGYI MED UNIV, DEPT MICROBIOL, SZEGED, HUNGARY
[4] EOTVOS LORAND UNIV, DEPT ORGAN CHEM, BUDAPEST, HUNGARY
[5] INST DRUG RES, BUDAPEST, HUNGARY
关键词
D O I
10.1111/j.1365-3083.1994.tb03512.x
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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-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 the conjugate-, peptide- and carrer-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.
引用
收藏
页码:609 / 617
页数:9
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