Schirmbeck R, Böhm W, Ando K, Chisari F V, Reimann J
Institute of Medical Microbiology, University of Ulm, Germany.
J Virol. 1995 Oct;69(10):5929-34. doi: 10.1128/JVI.69.10.5929-5934.1995.
The efficiency of different vaccination techniques to prime in vivo major histocompatibility complex class I-restricted murine cytotoxic T-lymphocyte (CTL) precursors to hepatitis B virus small surface antigen (HBsAg) was investigated. Mice were immunized either by injection of a low dose of recombinant HBsAg protein preparations (native HBsAg particles or denatured HBsAg monomers) without adjuvants, by infection with recombinant vaccinia virus carrying an HBsAg-encoding gene, or by intramuscular transfer of plasmid DNA encoding HBsAg under appropriate promoter control. In H-2d mice, an Ld-restricted, S28-39-specific CTL response was efficiently primed by all alternative vaccination techniques tested, but the most potent priming of class I-restricted CTL to HBsAg in vivo was observed with DNA immunization. Priming of anti-HBsAg CTL in H-2b mice was not detectable after infection with a recombinant vaccinia virus or after injection with exogenous recombinant HBsAg preparations. After DNA immunization, however, both Kb- and Db-restricted CTL reactivity to HBsAg emerged in H-2b mice. Hence, nucleic acid immunization revealed class I-restricted CTL responsiveness to HBsAg in a mouse strain previously considered to be a nonresponder at the CTL level. These results demonstrate that the simple technique of nucleic acid immunization not only is extremely efficient but also reveals an extended spectrum of potentially immunogenic epitopes of protein antigens.
研究了不同疫苗接种技术在体内激发主要组织相容性复合体I类限制性小鼠细胞毒性T淋巴细胞（CTL）前体针对乙型肝炎病毒小表面抗原（HBsAg）的效率。小鼠通过以下方式免疫：注射低剂量无佐剂的重组HBsAg蛋白制剂（天然HBsAg颗粒或变性HBsAg单体）；感染携带HBsAg编码基因的重组痘苗病毒；或在适当启动子控制下进行肌肉内转移编码HBsAg的质粒DNA。在H-2d小鼠中，所有测试的替代疫苗接种技术均能有效激发Ld限制性、S28-39特异性CTL反应，但在体内对HBsAg的I类限制性CTL的最有效激发是通过DNA免疫观察到的。在用重组痘苗病毒感染或注射外源性重组HBsAg制剂后，未检测到H-2b小鼠中抗HBsAg CTL的激发。然而，在DNA免疫后，H-2b小鼠中出现了对HBsAg的Kb和Db限制性CTL反应性。因此，核酸免疫揭示了在以前被认为在CTL水平上无反应的小鼠品系中对HBsAg的I类限制性CTL反应性。这些结果表明，核酸免疫的简单技术不仅极其有效，而且揭示了蛋白质抗原潜在免疫原性表位的扩展谱。
