Fehr T, Skrastina D, Pumpens P, Zinkernagel R M
Institute of Experimental Immunology, Department of Pathology, University Hospital, Schmelzbergstrasse 12, CH-8091 Zürich, Switzerland.
Proc Natl Acad Sci U S A. 1998 Aug 4;95(16):9477-81. doi: 10.1073/pnas.95.16.9477.
Recombinant viral or virus-like particles offer new tools for vaccine development. This study investigated hepatitis B core antigen (HBcAg) capsids and RNA phage Qbeta 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 Qbeta 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 Qbeta phage coats. Thus, recombinant virus particles are suitable vaccine carriers for the introduction of foreign B cell epitopes, if precise structural requirements are fulfilled.
重组病毒或病毒样颗粒为疫苗开发提供了新工具。本研究调查了乙肝核心抗原(HBcAg)衣壳和RNA噬菌体Qβ外壳作为外源表位载体在小鼠中诱导抗体反应的情况。结果表明,HBcAg衣壳可诱导非T细胞依赖性(TI)抗体。我们发现这些颗粒表现为抗原特异性TI-1型(TI-1)抗原,与其他结构刚性的病毒类似。当将乙肝表面抗原(HBsAg)前S1结构域的一个5氨基酸长的表位引入HBc分子的最佳位置时,它也表现为TI-1抗原。通过在表位后进行补偿性缺失以保留HBcAg衣壳的规则结构并使外源表位高度重复地暴露于表面,可实现对外源表位抗体反应的最佳效率。对于重组Qβ噬菌体外壳,当外源表位在Qβ噬菌体外壳的颗粒衍生物上重复表达时,对外源表位的抗体反应效率更高。因此,如果满足精确的结构要求,重组病毒颗粒是引入外源B细胞表位的合适疫苗载体。