Chen S C, Jones D H, Fynan E F, Farrar G H, Clegg J C, Greenberg H B, Herrmann J E
Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
J Virol. 1998 Jul;72(7):5757-61. doi: 10.1128/JVI.72.7.5757-5761.1998.
DNA vaccines are usually given by intramuscular injection or by gene gun delivery of DNA-coated particles into the epidermis. Induction of mucosal immunity by targeting DNA vaccines to mucosal surfaces may offer advantages, and an oral vaccine could be effective for controlling infections of the gut mucosa. In a murine model, we obtained protective immune responses after oral immunization with a rotavirus VP6 DNA vaccine encapsulated in poly(lactide-coglycolide) (PLG) microparticles. One dose of vaccine given to BALB/c mice elicited both rotavirus-specific serum antibodies and intestinal immunoglobulin A (IgA). After challenge at 12 weeks postimmunization with homologous rotavirus, fecal rotavirus antigen was significantly reduced compared with controls. Earlier and higher fecal rotavirus-specific IgA responses were noted during the peak period of viral shedding, suggesting that protection was due to specific mucosal immune responses. The results that we obtained with PLG-encapsulated rotavirus VP6 DNA are the first to demonstrate protection against an infectious agent elicited after oral administration of a DNA vaccine.
DNA疫苗通常通过肌肉注射或利用基因枪将包被DNA的颗粒递送至表皮来给予。将DNA疫苗靶向黏膜表面以诱导黏膜免疫可能具有优势，口服疫苗对于控制肠道黏膜感染可能有效。在一个小鼠模型中，我们用包裹在聚（丙交酯-乙交酯）（PLG）微粒中的轮状病毒VP6 DNA疫苗进行口服免疫后获得了保护性免疫反应。给予BALB/c小鼠一剂疫苗可诱导产生轮状病毒特异性血清抗体和肠道免疫球蛋白A（IgA）。在免疫后12周用同源轮状病毒攻击后，与对照组相比，粪便中的轮状病毒抗原显著减少。在病毒排出的高峰期观察到更早且更高的粪便轮状病毒特异性IgA反应，这表明保护作用归因于特异性黏膜免疫反应。我们用PLG包裹的轮状病毒VP6 DNA所获得的结果首次证明了口服DNA疫苗后可对感染因子产生保护作用。
