Abstract
摘要: 黏膜免疫反應與一般經由注射的免疫反應有些不同,主要誘發的抗體為 IgA,而且又比全身性注射的免疫反應較容易誘發耐受性。但是,黏膜給予的疫苗由於較方便,所以如果能夠找到一個較好的方法來誘發黏膜反應,將能夠讓疫苗更容易推廣和普及。在此一研究計劃中我們將建立各種免疫評估方法來研究此一黏膜疫苗的效果,所以在此一核心計畫中我們將分別建立方法來測定在此整合計畫中所使用的各種疫苗在致敏後所誘發的免疫反應。我們在前一年的計畫中已經建立相關的免疫評估方法,在未來三年的計畫中我們將研發在黏膜反應更有效的佐劑,包括利用各種方法來找出更有效的佐劑來應用到黏膜的疫苗上。此外,我們也將研究是否能夠利用奈米技術來遞送黏膜疫苗,讓這些疫苗能夠刺激較高的免疫反應。 Aim 1:在此一研究計畫中此一核心計畫主要是要建立各種免疫方法來評估黏膜免疫反應,我們在去年的計畫中已經初步建立這些相關的方法。我們在今年度的計畫中除了原本的方法外,我們也將支援其他子計畫進行黏膜疫苗給予後的黏膜組織基因表現,尤其是著重於這些黏膜組織的細胞激素和訊息傳導基因的表現情形,我們可以更進一步了解在黏膜免疫反應中主要參與的免疫細胞種類。對黏膜免疫反應有更清楚的了解,我們可以研發出更有效的黏膜疫苗。 Aim 2:我們在此一研究計畫中將設法找出促進黏膜免疫反應更有效的佐劑,尤其是針對在黏膜組織中表現較高的一些 innate immune 的相關受體如 toll-like receptors 或是 C-type lectin receptor,再利用其表現較高受體的結合根來作為可能的黏膜免疫疫苗的佐劑。我們將利用這些相關受體的結合根來進行相關的免疫注射,以找出較有效的黏膜疫苗佐劑。 Aim 3:我們也將進一步研究是否能夠利用奈米技術的方式讓這些黏膜疫苗可以更有效地在黏膜組織被吸收和誘發免疫反應,因此我們在這三年的計畫中將與相關的研究單位合作來利用奈米相關技術來給予這些黏膜疫苗,以瞭解是否能夠在黏膜組織有較好的吸收,而可以刺激較好的黏膜免疫反應。 在此一計畫中,主要是要研發能夠誘發較佳免疫反應的黏膜疫苗,因此本計畫將是此一研究計畫的核心計畫。在此一核心實驗室中我們將要建立各種疫苗的免疫反應測定方法,其中主要包括血中抗原特異性抗體濃度測定、抗原特異性的 T 細胞增殖反應、T 細胞製造細胞激素的情形、抗原特異性抗體分泌的 B細胞頻率測定和不同細胞激素製造的T 細胞頻率。同時,也要建立樹突細胞培養的平台來分析用在黏膜疫苗中來增進免疫反應的物質,以找出更多有效刺激黏膜免疫反應的物質。此外,此一核心計畫也將配合子計畫中的研究內容,來找出更好的黏膜疫苗。
Abstract: Mucosal immune response is somewhat different from systemic immune response by predominantly producing IgA antibody. In addition, the phenomenom of mucosal tolerance has been documented in many studies. It is critical to explore the methods which are able to induce better immune response instead of mucosal tolerance. In the previous project, we have established the methods of assaying both cellular and humoral immune response to support all the sub-projects in the integrated project. In this project, in addition to the immune assay we also like to explore the possible potent adjuvant for mucosal vaccines. Further, the application of nanoparticle will be also investigated. Aim 1: We like to establish the methods of immunoassays to assess both T and B cells function. In addition, we also like to support the other sub-projects in measuring cytokine genes or T cells-related genes expression profile of local mucosal tissue as the pattern of immunization with the real-time PCR. In addition, we also like to establish the methods to analyze the certain genes such as Toll-like receptor or C-type lectin receptor expression of mucosal tissues to identify the important innate immune cells receptors involved in the mucosal immune responses. Aim 2: We like to explore the potent adjuvants for mucosal vaccines. In the past one year’s project, the collaborative groups have applied different adjuvants such as Flt-3 ligand, GM-CSF, Flagellin to enhance the mucosal immune responses. However, the more potent adjuvants are needed for the development of mucosal vaccines. We aim to study the expression pattern of Toll-like receptors and C-type lectin receptors, ligands against these receptors will be used as the adjuvants for mucosal vaccines. Aim 3: We aim to apply the nanoparticle to deliver the mucosal vaccine to local action site to induce higher immune response with mucosal vaccine. In addition to the development of effector molecules as the adjuvant for mucosal vaccine, we also aim to study the effect of nanoparticle for enhancing mucosal immune response. The application of nanoparticles might be of help in enhancing immune responses through inhalation or intranasal route. We also like to use the in vitro cultured dendritic cells to screen the possible compounds derived from the pathogens as the potential adjuvants. In the last year’s project, we have set up the methods to determine antigen-specific antibodies of different isotypes, antigen-specific T cell proliferative response and also cytokine profile of antigen-stimulated T cells. We also like to identify the potential adjuvants for the application of mucosal vaccine and also the nanoparticle for the delivery of these mucosal vaccines. The dendritic cells culture for the screening the potential mucosal immunity enhancing reagents will be also established in this core sub-project. We believe the core sub-project here could provide the best supportive role for the integrated project of mucosal vaccine development.
Keyword(s)
黏膜疫苗
抗體測定
T細胞增生反應
mucosal vaccine
antigen-specific antibody
antigen-specific B cells
antigen-specific T cells