T cell-independent type I antibody response against B cell epitopes expressed repetitively on recombinant virus particles

被引:137
作者
Fehr, T
Skrastina, D
Pumpens, P
Zinkernagel, RM
机构
[1] Univ Zurich Hosp, Dept Pathol, Inst Expt Immunol, CH-8091 Zurich, Switzerland
[2] Latvian State Univ, Biomed Res & Study Ctr, LV-1067 Riga, Latvia
关键词
D O I
10.1073/pnas.95.16.9477
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Recombinant viral or virus-like particles offer new tools for vaccine development. This study investigated hepatitis B core antigen (HBcAg) capsids and RNA phage Q beta coats as carriers of a foreign epitope to induce antibody responses in mice. HBcAg capsids were shown to induce T cell-independent (TI) antibodies. We found that these particles behave as antigen-specific TI type 1 (TI-1) Ag comparable to other rigidly structured viruses. When a 5-aa long epitope of the pre-S1 domain of hepatitis B surface antigen (HBsAg) was introduced into the optimal position of the HBc molecule, it also behaved as a TI-1 Ag, Best efficiency of the antibody response to the foreign epitope was achieved by a compensatory deletion after the epitope to retain the regular structure of the HBcAg capsid with a highly repetitive superficial exposition of the foreign epitope, For recombinant Q beta phage coats, a much more efficient antibody response to the foreign epitope was achieved when the foreign epitope was expressed repetitively on a particulate derivate of Q beta phage coats. Thus, recombinant virus particles are suitable vaccine carriers for the introduction of foreign B cell epitopes, if precise structural requirements are fulfilled.
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页码:9477 / 9481
页数:5
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