Matrix-M™ adjuvant induces local recruitment, activation and maturation of central immune cells in absence of antigen.
Matrix-M™ adjuvant induces local recruitment, activation and maturation of central immune cells in absence of antigen.
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DOI：
10.1371/journal.pone.0041451
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Stertman L
中科院分区：
文献类型：
--
作者：
Reimer JM;Karlsson KH;Lövgren-Bengtsson K;Magnusson SE;Fuentes A;Stertman L
皂苷类佐剂被广泛用于增强体液免疫和细胞免疫对疫苗抗原的免疫应答，尽管目前还不完全清楚它们是如何调节其刺激作用的。本研究以明胶为参比佐剂，探讨无抗原的基质-M™佐剂的作用机制。佐剂基质-M™由40纳米纳米颗粒组成，由Quillaja皂苷、胆固醇和磷脂组成。BALB/c小鼠皮下注射一次、3、12和30µg的Matrix-M™，48h后白细胞向引流淋巴结和脾内募集。流式细胞仪分析表明CD11b+Gr-1高颗粒细胞是DLN和脾中细胞数量增加最多的细胞群。此外，树突状细胞、F4/80int细胞、T细胞、B细胞和NK细胞被募集到DLN中，脾中F4/80int细胞的数量增加，B细胞和树突状细胞也有一定程度的增加。DLN中T细胞、B细胞、NK细胞、CD11b+Gr-1高表达细胞、F4/80int细胞和树突状细胞表达早期活化标志CD69水平升高。在脾组织中，CD69主要表达于NK细胞。B细胞和树突状细胞表达协同刺激分子CD86，树突状细胞表达高水平的MHCII类分子。大剂量(30µg)的Matrix-M™在给药4h后可诱导可检测到的血清IL-6和β-1水平，很可能代表局部产生的细胞因子的溢出。12µg Matrix-M™给药后，血清IL-6水平也略有升高。综上所述，基质-M™单独具有早期免疫刺激特性，因为治疗剂量导致局部一过性免疫反应，中央免疫细胞向DLN募集和激活。这些效应可能在增强疫苗抗原的摄取和呈递以引发合格的免疫反应方面发挥作用。
Saponin-based adjuvants are widely used to enhance humoral and cellular immune responses towards vaccine antigens, although it is not yet completely known how they mediate their stimulatory effects. The aim of this study was to elucidate the mechanism of action of adjuvant Matrix-M™ without antigen and Alum was used as reference adjuvant. Adjuvant Matrix-M™ is comprised of 40 nm nanoparticles composed of Quillaja saponins, cholesterol and phospholipid. BALB/c mice were subcutaneously injected once with, 3, 12 or 30 µg of Matrix-M™, resulting in recruitment of leukocytes to draining lymph nodes (dLNs) and spleen 48 h post treatment. Flow cytometry analysis identified CD11b+ Gr-1high granulocytes as the cell population increasing most in dLNs and spleen. Additionally, dendritic cells, F4/80int cells, T-, B- and NK-cells were recruited to dLNs and in spleen the number of F4/80int cells, and to some extent, B cells and dendritic cells, increased. Elevated levels of early activation marker CD69 were detected on T-, B- and NK-cells, CD11b+ Gr-1high cells, F4/80int cells and dendritic cells in dLNs. In spleen CD69 was mainly up-regulated on NK cells. B cells and dendritic cells in dLNs and spleen showed an increased expression of the co-stimulatory molecule CD86 and dendritic cells in dLNs expressed elevated levels of MHC class II. The high-dose (30 µg) of Matrix-M™ induced detectable serum levels of IL-6 and MIP-1β 4 h post administration, most likely representing spillover of locally produced cytokines. A lesser increase of IL-6 in serum after administration of 12 µg Matrix-M™ was also observed. In conclusion, early immunostimulatory properties were demonstrated by Matrix-M™ alone, as therapeutic doses resulted in a local transient immune response with recruitment and activation of central immune cells to dLNs. These effects may play a role in enhancing uptake and presentation of vaccine antigens to elicit a competent immune response.
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DOI：
10.4049/jimmunol.0900164
发表时间：
2009-10-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
McKee AS;Munks MW;MacLeod MK;Fleenor CJ;Van Rooijen N;Kappler JW;Marrack P
通讯作者：
Marrack P
DOI：
10.1007/bf01240612
发表时间：
1974-01-01
期刊：
ARCHIV FUR DIE GESAMTE VIRUSFORSCHUNG
影响因子：
--
作者：
DALSGAARD, K
通讯作者：
DALSGAARD, K
感染期间淋巴结中中性粒细胞迁移的动态。
影响因子：
32.4
作者：
Chtanova, Tatyana;Schaeffer, Marie;Han, Seong-Ji;van Dooren, Giel G.;Nollmann, Marcelo;Herzmark, Paul;Chan, Shiao Wei;Satija, Harshita;Camfield, Kristin;Aaron, Holly;Striepen, Boris;Robey, Ellen A.
通讯作者：
Robey, Ellen A.
DOI：
10.1084/jem.20081571
发表时间：
2009-01-16
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Dienz O;Eaton SM;Bond JP;Neveu W;Moquin D;Noubade R;Briso EM;Charland C;Leonard WJ;Ciliberto G;Teuscher C;Haynes L;Rincon M
通讯作者：
Rincon M
影响因子：
3.8
作者：
Behboudi, S;Morein, B;VillacresEriksson, M
通讯作者：
VillacresEriksson, M