利用Flt3L或GM-CSF基因增強腸病毒DNA疫苗誘發之黏膜免疫反應

Abstract

腸病毒71型(EV71)是在世界各地腸病毒的感染中，造成高致死率以及嚴重的神經方面疾病最主要的病毒。由於至今仍無有效的方法治療受腸病毒71型感染的病患，發展並增強DNA疫苗的效用以提高體內免疫反應，對於預防腸病毒71型的感染也許是有效的方法。DNA疫苗所引起的免疫反應是由抗原呈現細胞(APC)，尤其是樹突細胞，呈現抗原開始。Flt3L與GM-CSF這兩種細胞激素對於樹突細胞的發育以及生長都扮演了相當重要的角色。在本研究中，使用EV71 vp1質體合併使用Flt3L或GM-CSF細胞激素的基因作為佐劑，經由鼻腔的途徑給予質體以致敏Balb/c小鼠，並觀察後續所誘發之免疫反應。本研究提出經由黏膜(鼻腔內)途徑給予小鼠vp1質體伴隨Flt3L佐劑使用時，可以誘導出小鼠體內抗VP1特異性IgA抗體的產生。經由vp1與Flt3L致敏之小鼠體內血清中之IgA含量明顯的高於未經處理的組別。本篇研究的結果指出，合併使用Flt3L基因與腸病毒71型vp1基因持續致敏小鼠，可以增加小鼠體內特異性抗體的產生，並且引發較強的黏膜免疫反應，提供保護的機制以減少受到腸病毒之感染機率。

Enterovirus 71(EV71) has been the most important enterovirus to cause the high fatality and severe neurological diseases. Due to the fact that there is still no appropriate treatment to remedy patients after they are infected, efficient DNA vaccine might be an effective approach to induce immune response against EV71 infections. Immune responses generated by DNA vaccination are initiated by antigen-presenting cells (APCs), especially dendritic cells. Both FMS-like tyrosine kinase 3 ligand(Flt3L) and granulocyte-macrophage colony stimulating factor(GM-CSF) proteins play crucial roles in the development and expansion of dendritic cells, the professional APCs. In this study, we immunized female Balb/c mice with EV71 vp1 plasmid DNA and co-immunize with or without Flt3L or GM-CSF genes as the adjuvant genes by intranasal administration. We demonstrated that immunization with vp1 plasmid DNA accompanies with Flt3L adjuvant gene via mucosal (intranasal) route could induce higher anti-VP1 specific IgA production. Balb/c mice immunized with vp1 and Flt3L plasmids had much higher seral IgA titer than that of untreated group. Our result indicated that the combination of Flt3L gene with enteroviral vp1 gene immunization enhanced antibody production and triggered a better mucosa immune response for protection from enteroviral infection.