Eliciting Dual-Niche Immunological Priming by Acupoint Delivery of Nanovaccines
Corresponding Author: Chunhai Fan
Nano-Micro Letters,
Vol. 17 (2025), Article Number: 280
Abstract
Immunization has long played essential roles in preventing diseases. However, the desire for precision delivery of vaccines to boost a robust immune response remains largely unmet. Here, we describe the use of acupoint delivery of nanovaccines (ADN) to elicit dual-niche immunological priming. ADN can simultaneously stimulate mast cell-assisted maturation of dendritic cells at the acupoint and enable direct delivery of nanovaccines into the draining lymph nodes. We demonstrate that ADN not only provokes antigen presentation by lymph node-resident CD8α+ dendritic cells, but also induces the accumulation of nanovaccines in B-cell zones, amplifying antigen-specific cytotoxic T lymphocyte responses and immunoglobulin G antibody expression in draining lymph nodes. ADN also generates systemic immune responses by causing immune memory and preventing T-cell anergy in the spleen. Further supported by evoking effective antitumor responses and high-level antiviral antibodies in mice, ADN provides a simple yet versatile platform for advanced nanovaccination.
Highlights:
1 We report the use of acupoint delivery of nanovaccines (NVs) to elicit a dual-niche immunological priming by simultaneously stimulating mast cell-assisted maturation of CD11b+ dendritic cells (DCs) at the acupoint and directly enriching NVs into the draining lymph nodes (dLNs).
2 The dual-niche immunological priming not only provokes antigen presentation by LN-resident CD8α+ DCs, but also induces the accumulation of NVs in B-cell zones, highlights a facile yet versatile platform for advanced nanovaccination toward tumor therapy and infection prevention.
Keywords
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References
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R. Torres-Rosas, G. Yehia, G. Peña, P. Mishra, M. del Rocio Thompson-Bonilla et al., Dopamine mediates vagal modulation of the immune system by electroacupuncture. Nat. Med. 20(3), 291–295 (2014). https://doi.org/10.1038/nm.3479
H. Jin, Y. Wu, S. Bi, Y. Xu, F. Shi et al., Higher immune response induced by vaccination in Houhai acupoint relates to the lymphatic drainage of the injection site. Res. Vet. Sci. 130, 230–236 (2020). https://doi.org/10.1016/j.rvsc.2020.03.018
L. Wang, X. Wang, F. Yang, Y. Liu, L. Meng et al., Systemic antiviral immunization by virus-mimicking nanops-decorated erythrocytes. Nano Today 40, 101280 (2021). https://doi.org/10.1016/j.nantod.2021.101280
S.J. Galli, S. Nakae, M. Tsai, Mast cells in the development of adaptive immune responses. Nat. Immunol. 6(2), 135–142 (2005). https://doi.org/10.1038/ni1158
P. Huang, H. Deng, Y. Zhou, X. Chen, The roles of polymers in mRNA delivery. Matter 5(6), 1670–1699 (2022). https://doi.org/10.1016/j.matt.2022.03.006
Y. Cao, X. Zhu, M.N. Hossen, P. Kakar, Y. Zhao et al., Augmentation of vaccine-induced humoral and cellular immunity by a physical radiofrequency adjuvant. Nat. Commun. 9(1), 3695 (2018). https://doi.org/10.1038/s41467-018-06151-y
J.J. Rennick, A.P.R. Johnston, R.G. Parton, Key principles and methods for studying the endocytosis of biological and nanop therapeutics. Nat. Nanotechnol. 16(3), 266–276 (2021). https://doi.org/10.1038/s41565-021-00858-8
J.R. Gordon, S.J. Galli, Mast cells as a source of both preformed and immunologically inducible TNF-α/cachectin. Nature 346(6281), 274–276 (1990). https://doi.org/10.1038/346274a0
M.M. Amaral, C. Davio, A. Ceballos, G. Salamone, C. Cañones et al., Histamine improves antigen uptake and cross-presentation by dendritic cells. J. Immunol. 179(6), 3425–3433 (2007). https://doi.org/10.4049/jimmunol.179.6.3425
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