Smart combination of aluminum hydroxide and MF59 to induce strong cellular immune responses

被引：28

作者：

Chen, Zhengjun ^{[1
,2
]}

Hao, Xinyan ^{[1
,2
]}

Wang, Hairui ^{[1
,2
]}

Zhong, Xiaofang ^{[1
,2
]}

Chen, Xiaoyan ^{[1
,2
]}

Zhao, Yuanhao ^{[1
,2
]}

Zhang, Yuandong ^{[1
,2
]}

Du, Guangsheng ^{[1
,2
]}

Sun, Xun ^{[1
,2
]}

机构：

[1] Sichuan Univ, West China Sch Pharm, Sichuan Engn Lab Plant Sourced Drug, Key Lab Drug Targeting & Drug Delivery Syst Educ M, Chengdu 610041, Peoples R China

[2] Sichuan Univ, West China Sch Pharm, Sichuan Res Ctr Drug Precis Ind Technol, Chengdu 610041, Peoples R China

来源：

JOURNAL OF CONTROLLED RELEASE | 2022年 / 349卷

基金：

中国国家自然科学基金;

关键词：

Nanovaccine; CD8(+) T cell responses; Aluminum hydroxide; MF59; Adjuvant; LYMPH-NODE; CANCER-IMMUNOTHERAPY; DENDRITIC CELLS; DRUG EXPOSURE; ADJUVANT; ANTIGEN; ADSORPTION; MICELLES; IMPROVE;

D O I：

10.1016/j.jconrel.2022.07.032

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

As two of the most widely used adjuvants, aluminum hydroxide and the oil-in-water emulsion MF59 have their intrinsic limitations: classical aluminum gel induces only weak cellular immune responses while MF59 cannot be used as an antigen delivery system due to its poor physical interaction with antigen molecules. Herein, we combined these two adjuvants and constructed a novel nano-vaccine delivery system by inserting aluminum hydroxide into the surface of a modified MF59 nano-emulsion (AlNEs). A model antigen ovalbumin (OVA) and an immune potentiator CpG were adsorbed on the surface of AlNEs (hereinafter AlNEs-OVA-CpG) through a facile mixing step. After subcutaneous injection, AlNEs-OVA-CpG effectively drained to lymph nodes, delivered both cargos into lymph node-resident antigen presenting cells (APCs), and escaped from lysosomes into the cytoplasm, resulting in enhanced antigen cross-presentation. Finally, AlNEs-OVA-CpG induced potent antigen-specific humoral and cellular immune responses, which significantly inhibited tumor growth and prolonged mice survival in a EG7-OVA tumor model. In sum, our results suggested that AlNEs have a great prospect to induce CD8(+) T cell responses for subunit antigens.

引用

页码：699 / 711

页数：13

共 49 条

[11] ENHANCED IN-VIVO GROWTH AND RESISTANCE TO REJECTION OF TUMOR-CELLS EXPRESSING DOMINANT-NEGATIVE IFN-GAMMA RECEPTORS [J].