Boyle J S, Brady J L, Lew A M
Autoimmunity and Transplantation Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.
Nature. 1998 Mar 26;392(6674):408-11. doi: 10.1038/32932.
Viral infection and vaccination with DNA both induce similar immune responses to encoded antigens that are produced by the host. The availability of antigens in lymphoid organs is important in generating an immune response to viral challenge. Antigen availability may also be important in the response to DNA vaccines, because immune responses are stronger when antigen is secreted from DNA-transfected cells. We directed antigen to lymphoid organs by vaccination with DNA encoding antigen-ligand fusion proteins. The two ligands examined bind to receptors that are present on high endothelial venule cells of lymph nodes or on antigen-presenting cells. Here we show that both the humoral and the cellular immune responses to a model DNA vaccine were enhanced using either antigen-targeting strategy. Moreover, directing antigen to antigen-presenting cells speeded up, and altered the form of, the immune response. Directing antigen to sites of immune-response induction may represent a generic means of tailoring a potent and effective immune response to a DNA vaccine.
病毒感染和DNA疫苗接种都会诱导宿主产生针对所编码抗原的相似免疫反应。淋巴器官中抗原的可利用性对于产生针对病毒攻击的免疫反应很重要。抗原的可利用性在对DNA疫苗的反应中可能也很重要,因为当抗原从DNA转染细胞中分泌出来时免疫反应会更强。我们通过接种编码抗原-配体融合蛋白的DNA将抗原导向淋巴器官。所检测的两种配体可与淋巴结高内皮微静脉细胞或抗原呈递细胞上存在的受体结合。在此我们表明,使用任何一种抗原靶向策略均可增强对模型DNA疫苗的体液免疫和细胞免疫反应。此外,将抗原导向抗原呈递细胞可加快免疫反应并改变其形式。将抗原导向免疫反应诱导部位可能是一种针对DNA疫苗定制有效且强力免疫反应的通用方法。