Hahn Ulrike K, Alex Michaela, Czerny Claus-Peter, Böhm Reinhard, Beyer Wolfgang
Institut für Umwrelt-und Tierhygiene, University of Hohenheim, Garbenstr. 30, Stuttgart 70599, Germany.
Int J Med Microbiol. 2004 Jul;294(1):35-44. doi: 10.1016/j.ijmm.2003.12.002.
Immune responses against the protective antigen (PA) of Bacillus anthracis are known to confer immunity against anthrax. We evaluated the efficacy of genetic vaccination with plasmid vectors encoding PA, in protecting mice from a lethal challenge with B. anthracis STI spores. BALB/c and A/J mice were immunized via gene gun inoculation, using eukaryotic expression vectors with different cellular targeting signals for the encoded antigen. The vector pSecTag PA83, encoding the full-length PA protein, has a signal sequence for secretion of the expressed protein. The plasmids pCMV/ER PA83 and pCMV/ER PA63, encoding the full-length and the physiologically active form of PA, respectively, target and retain the expressed antigen in the endoplasmic reticulum of transfected cells. All three plasmids induced PA-specific humoral immune responses, predominantly IgG1 antibodies, in mice. Spleen cells collected from plasmid-vaccinated BALB/c mice produced PA-specific interleukin-4, interleukin-5, and interferon-gamma in vitro. Vaccination with either pSecTag PA83 or pCMV/ER PA83 showed significant protection of A/J mice against infection with B. anthracis STI spores.
已知针对炭疽芽孢杆菌保护性抗原(PA)的免疫反应可赋予抗炭疽免疫力。我们评估了用编码PA的质粒载体进行基因疫苗接种在保护小鼠免受炭疽芽孢杆菌STI孢子致死性攻击方面的效果。通过基因枪接种,使用针对编码抗原具有不同细胞靶向信号的真核表达载体,对BALB/c和A/J小鼠进行免疫。编码全长PA蛋白的载体pSecTag PA83具有表达蛋白分泌的信号序列。分别编码全长PA和生理活性形式PA的质粒pCMV/ER PA83和pCMV/ER PA63,将表达的抗原靶向并保留在转染细胞的内质网中。所有这三种质粒均在小鼠中诱导了PA特异性体液免疫反应,主要是IgG1抗体。从接种质粒的BALB/c小鼠收集的脾细胞在体外产生了PA特异性白细胞介素-4、白细胞介素-5和干扰素-γ。用pSecTag PA83或pCMV/ER PA83进行疫苗接种显示对A/J小鼠感染炭疽芽孢杆菌STI孢子具有显著的保护作用。