Novel adjuvant delivery system constructed by alum-emulsion hybrid nanoparticles with TLR9 agonists boosts vaccine immunity
Vaccine Adjuvant Delivery Systems (VADSs) that integrate both delivery and adjuvancy constitute a vital strategy in modern vaccine research. Herein, we employed microfluidics to blend nanosized aluminum hydroxide (XA) and a nanoemulsion (XE) in varying proportions. A 2:3 (v/v) mixture produced nanoparticles (XAE) of approximately 220 nm with near-neutral zeta potential, which significantly enhanced antigen uptake in DC2.4 cells and displayed stronger adjuvant activity than XA or XE alone. By electrostatically adsorbing the TLR9 agonist CpG onto XAE, we constructed XAEC as an integrated delivery platform that co-delivers antigens and immune-stimulatory molecules, thereby improving CpG's bioavailability and biocompatibility. This XAEC platform generated an "immune-activated microenvironment" at the injection site, fostering antigen-presenting cell (APC) recruitment, augmenting antigen presentation, facilitating vaccine trafficking to immune organs, and eliciting a Th1-biased immune response. XAEC substantially boosted immunogenicity in prophylactic Respiratory Syncytial Virus (RSV) and Varicella-Zoster Virus (VZV) vaccines and induced potent antitumor responses in a Human Papillomavirus (HPV) tumor model. Hence, XAEC emerges as a promising next-generation vaccine adjuvant system.
Authors
- Ciying Qian (ORCID: https://orcid.org/0000-0002-5304-6147)
- Hai Yu (ORCID: https://orcid.org/0000-0002-4378-0532)
- Qingbing Zheng (ORCID: https://orcid.org/0000-0002-7516-9965)
- Renfei Gao (ORCID: https://orcid.org/0000-0003-4867-842X)
- Rong Su (ORCID: https://orcid.org/0000-0003-0776-3716)
- Jialin Xu (ORCID: https://orcid.org/0000-0002-3910-1306)
- Sibo Zhang (ORCID: https://orcid.org/0000-0002-3869-0380)
- Ningshao Xia
- Ying Gu (ORCID: https://orcid.org/0000-0001-8900-1381)
- Zizheng Zheng (ORCID: https://orcid.org/0000-0003-0099-4212)
- Lizhi Zhou (ORCID: https://orcid.org/0000-0001-6225-4303)
- Xueqing Zhu
- Xiuli Zhang (ORCID: https://orcid.org/0000-0001-9090-6153)
- Jun Zhang (ORCID: https://orcid.org/0000-0002-6601-9180)
- Shao-wei Li (ORCID: https://orcid.org/0000-0002-3276-1037)
- Feng Han (ORCID: https://orcid.org/0000-0002-9337-7936)
- Yufang Li (ORCID: https://orcid.org/0000-0003-3337-7616)
- Min Lin (ORCID: https://orcid.org/0000-0001-8496-0479)
- Yarong Zeng
- Tingting Li (ORCID: https://orcid.org/0009-0003-4233-0702)
- Feihong Zou
- Yifan Yin (ORCID: https://orcid.org/0009-0008-5382-478X)
Institutions
- Xiamen University (CN)
Publication Details
- Journal
- Journal of Nanobiotechnology
- Published
- 2025-07-01
- DOI
- https://doi.org/10.1186/s12951-025-03560-2
- Citations
- 2
- Primary Topic
- Immunotherapy and Immune Responses
- Type
- article
- Field-Weighted Citation Impact
- 1.59
Funders
- National Natural Science Foundation of China
- Natural Science Foundation of Fujian Province
- National Key Research and Development Program of China
- Fundamental Research Funds for the Central Universities