Chen S C, Fynan E F, Robinson H L, Lu S, Greenberg H B, Santoro J C, Herrmann J E
Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester 01655, USA.
Vaccine. 1997 Jun;15(8):899-902. doi: 10.1016/s0264-410x(96)00272-1.
It is estimated that Group A rotavirus diarrhea causes as many as one million deaths per year in children worldwide, and effective vaccines will be essential for their control. Plasmid DNA vaccines encoding murine rotaviral proteins VP4, VP6, or VP7 were tested in adult BALB/c mice for their ability to induce immune responses and provide protection against rotavirus challenge. The vaccines were administered by inoculation into cells of the epidermis with an Accell gene gun. (Auragen, Inc., Middleton, WI, USA). Each vaccine elicited rotavirus-specific serum antibodies as measured by ELISA. Virus neutralizing antibodies were detected in mice receiving plasmid DNAs encoding for outer capsid proteins VP4 and VP7, but not for VP6, an inner capsid protein, and all of the vaccines generated virus-specific CTL responses. Each vaccine was effective in protecting mice against infection after homotypic rotavirus (100 ID50) challenge, showing reductions (P < 0.0002) in viral excretion measured over a 9 day period. Increased rotavirus-specific intestinal IgA antibodies were seen in vaccinated mice after rotavirus challenge, particularly in mice that received the VP6 DNA vaccine. This suggests that intracellular IgA-mediated neutralization may be involved in protective immunity induced by the VP6 DNA vaccine, and may represent a new mechanism for protection by DNA vaccines.
据估计，全球范围内，A组轮状病毒腹泻每年导致多达100万儿童死亡，有效的疫苗对于控制该病至关重要。对编码鼠轮状病毒蛋白VP4、VP6或VP7的质粒DNA疫苗在成年BALB/c小鼠中进行了测试，以评估其诱导免疫反应及提供针对轮状病毒攻击的保护能力。通过使用Accell基因枪（美国威斯康星州米德尔顿的Auragen公司）接种到表皮细胞中来施用疫苗。通过ELISA检测，每种疫苗均能引发轮状病毒特异性血清抗体。在接受编码外衣壳蛋白VP4和VP7而非内衣壳蛋白VP6的质粒DNA的小鼠中检测到病毒中和抗体，并且所有疫苗均产生了病毒特异性CTL反应。在同型轮状病毒（100 ID50）攻击后，每种疫苗均能有效保护小鼠免受感染，在9天的时间段内测量显示病毒排泄减少（P < 0.0002）。轮状病毒攻击后，接种疫苗的小鼠中轮状病毒特异性肠道IgA抗体增加，特别是接受VP6 DNA疫苗的小鼠。这表明细胞内IgA介导的中和作用可能参与了VP6 DNA疫苗诱导的保护性免疫，并且可能代表了DNA疫苗保护的一种新机制。
