Hepatitis B virus surface antigen (HBsAg) as carrier for synthetic peptides having an attached hydrophobic tail.
Hepatitis B virus surface antigen (HBsAg) as carrier for synthetic peptides having an attached hydrophobic tail.
复制标题
乙型肝炎病毒表面抗原 (HBsAg) 作为具有附着的疏水尾部的合成肽的载体。
DOI:
10.1016/0161-5890(89)90020-5
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发表时间:
1989
影响因子:
3.6
通讯作者:
Girard,M
中科院分区:
文献类型:
--
作者:
Neurath,AR;Strick,N;Girard,M
B- and T-cell epitopes from three distinct regions of the hepatitis B virus (HBV) envelope (env) protein (preS1, preS2 and S) are involved in eliciting protective immunity. Since preS1 sequences inhibit the secretion of HBV env proteins from eukaryotic cells, it is difficult to prepare immunogens rich in preSl sequences. This problem can be overcome by linking synthetic peptides from the preS1 region to particles containing both S and preS2 sequences. We describe here a novel approach for bincling of synthetic peptides to exposed hydrophobic domains on HBV env proteins. Long chain fatty acids or mercaptans are covalently linked to synthetic peptides. Peptides with the attached hydrophobic tails interact strongly with HBV env proteins (S + preS2), whereby hybrid immunogens are generated. Such immunogens can be used in combination with alum, the only adjuvant approved for human use. The combination of the preS1 peptide [preS(12–47)] with particles containing the S and preS2 regions resulted in an immunogen which: (1) elicits a broad spectrum of protective antibodies; (2) circumvents the nonresponsiveness to: (a) preS1 epitopes in preS1-nonresponder strains of mice; and (b) S-protein in S-protein-nonresponder strains of mice; and (3) augments the immune response to S-protein. The combination of HBV env proteins with a synthetic peptide from the envelope of the human immunodeficiency virus (HIV-1) resulted in an immunogen eliciting anti-HIV-1. Hybrid immunogens consisting of viral proteins and of synthetic peptides represent a feasible approach for the design of future vaccines.