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已发表论文
由 TA/Mn2+ 网络稳定化的角鲨烯和 Mn2+ 纳米乳液可增强亚单位疫苗的免疫原性
Authors Chen K , Li L, Wang N, Deng Y, Xiang C, Zhang X, Zhou Y, Yang H, Xie Y, Chen X, Li Y, Li Y, Guo G, Shi Y
Received 7 May 2025
Accepted for publication 7 September 2025
Published 18 September 2025 Volume 2025:20 Pages 11341—11360
DOI https://doi.org/10.2147/IJN.S538737
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Dr Kamakhya Misra
Kai Chen,1 Linlin Li,1 Ning Wang,1 Yunfeng Deng,1 Chuanying Xiang,1 Xiaomin Zhang,1 Yangyang Zhou,1 Hong Yang,1 Yu Xie,1 Xiaoting Chen,2 Ying Li,3 Yan Li,1 Gang Guo,1 Yun Shi1
1Institute of Biopharmaceuticals, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Animal Experimental Center, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, People’s Republic of China
Correspondence: Yun Shi, Email shiyun@wchscu.cn
Background: Effective protection against infections requires humoral and cellular immune responses. Although current subunit vaccines primarily induce antibodies, they often fail to elicit strong CD8+ T cell responses. To overcome this challenge, we designed a dual-adjuvant nano-emulsion that integrates squalene (Sq) and Mn2+, using tannic acid (TA)/Mn2+ coordination networks for stabilization, serving as a potent immune-enhancing adjuvant system.
Methods: The ultrasonic emulsification was used to prepared nano-emulsion system (Sq@TA/Mn) combining Sq and Mn2+. The Sq@TA/Mn adsorbed ovalbumin (OVA) to form a Sq@TA/Mn@OVA vaccine. The cytotoxicity, ROS generation, cellular uptake, and distribution of the OVA vaccine were evaluated in DC2.4 cells. The retention of OVA vaccines in the site of injection of female C57BL/6 mice were studied using an imaging system. The mice were administered intramuscular injections of Sq@TA/Mn@OVA vaccine with prime-boost immunization strategies. The humoral immune and cellular immune responses were analysed with enzyme-linked immunosorbent assay (ELISA) and flow cytometry, respectively. We evaluated the nano-emulsion using a recombinant peptidoglycan-associated lipoprotein (rPal) antigen to create a Sq@TA/Mn@rPal vaccine against Acinetobacter baumannii-induced pneumonia.
Results: The Sq@TA/Mn nano-emulsion was constructed through ultrasonic emulsification. The nano-emulsion efficiently adsorbed OVA to form a Sq@TA/Mn@OVA vaccine. The OVA vaccine exhibited a favorable safety profile, enhanced ROS generation, dendritic cell uptake, and improved antigen retention at the injection site. Compared to Alum, this vaccine enhanced the production of OVA-specific antibodies and IFN-γ, promoted the expansion of spleen effector memory T cells, and increased the population of lung-resident memory T cells.The Sq@TA/Mn adjuvant elicited higher rPal-specific IgG, IgG1, and IgG2a titers and improved the protective efficacy against infection as compared with Alum.
Conclusion: This study provides a novel method for the co-delivery of Mn2+, Sq, and antigens. These results highlighted the potential of the Sq@TA/Mn platform as a versatile and effective adjuvant for enhancing subunit vaccines.
Keywords: nano-emulsion, Tannic acid/Mn2+ networks, adjuvant, vaccine, infection
1Institute of Biopharmaceuticals, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Animal Experimental Center, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, People’s Republic of China
Correspondence: Yun Shi, Email shiyun@wchscu.cn
Background: Effective protection against infections requires humoral and cellular immune responses. Although current subunit vaccines primarily induce antibodies, they often fail to elicit strong CD8+ T cell responses. To overcome this challenge, we designed a dual-adjuvant nano-emulsion that integrates squalene (Sq) and Mn2+, using tannic acid (TA)/Mn2+ coordination networks for stabilization, serving as a potent immune-enhancing adjuvant system.
Methods: The ultrasonic emulsification was used to prepared nano-emulsion system (Sq@TA/Mn) combining Sq and Mn2+. The Sq@TA/Mn adsorbed ovalbumin (OVA) to form a Sq@TA/Mn@OVA vaccine. The cytotoxicity, ROS generation, cellular uptake, and distribution of the OVA vaccine were evaluated in DC2.4 cells. The retention of OVA vaccines in the site of injection of female C57BL/6 mice were studied using an imaging system. The mice were administered intramuscular injections of Sq@TA/Mn@OVA vaccine with prime-boost immunization strategies. The humoral immune and cellular immune responses were analysed with enzyme-linked immunosorbent assay (ELISA) and flow cytometry, respectively. We evaluated the nano-emulsion using a recombinant peptidoglycan-associated lipoprotein (rPal) antigen to create a Sq@TA/Mn@rPal vaccine against Acinetobacter baumannii-induced pneumonia.
Results: The Sq@TA/Mn nano-emulsion was constructed through ultrasonic emulsification. The nano-emulsion efficiently adsorbed OVA to form a Sq@TA/Mn@OVA vaccine. The OVA vaccine exhibited a favorable safety profile, enhanced ROS generation, dendritic cell uptake, and improved antigen retention at the injection site. Compared to Alum, this vaccine enhanced the production of OVA-specific antibodies and IFN-γ, promoted the expansion of spleen effector memory T cells, and increased the population of lung-resident memory T cells.The Sq@TA/Mn adjuvant elicited higher rPal-specific IgG, IgG1, and IgG2a titers and improved the protective efficacy against infection as compared with Alum.
Conclusion: This study provides a novel method for the co-delivery of Mn2+, Sq, and antigens. These results highlighted the potential of the Sq@TA/Mn platform as a versatile and effective adjuvant for enhancing subunit vaccines.
Keywords: nano-emulsion, Tannic acid/Mn2+ networks, adjuvant, vaccine, infection