Key Takeaways & Executive Findings
- •• Acupoint delivery of nanovaccines (ADN) simultaneously stimulates mast cell-assisted dendritic cell maturation at the acupoint and directly enriches nanovaccines into draining lymph nodes, achieving dual-niche immunological priming. • ADN enhances antigen presentation by lymph node-resident CD8α+ dendritic cells and induces nanovaccine accumulation in B-cell zones, amplifying cytotoxic T lymphocyte responses and IgG antibody expression. • ADN generates systemic immune responses by inducing immune memory and preventing T-cell anergy in the spleen, leading to effective antitumor and antiviral immunity in mice. • This facile and versatile platform offers a promising strategy for advanced nanovaccination, potentially improving vaccine efficacy against tumors and infectious diseases.
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.
1. Introduction
Immunization is an important approach to prevent or even treat diseases by eliciting antigen-specific immune responses [1, 2]. Parenteral administration, particularly intramuscular (IM) injection, is widely applied for immunization [3]. Following injection, tissue-resident antigen-presenting cells (APCs) internalize vaccines and subsequently migrate to draining lymph nodes (dLNs) to induce antigen cross-presentation [4–6]. Simultaneously, a small portion of administered vaccines can directly diffuse into dLNs to elicit immunological priming [7–9]. However, insufficient distribution of APCs in the site of injection inevitably causes either limited transferring of antigens to dLN-resident APCs or inadequate cross-presentation to T cells in dLNs [10]. Meanwhile, the existence of multiple biological barriers at organ and sub-organ levels can filter the majority of administered vaccines, largely impeding their direct accumulation in dLNs [11]. Consequently, intramuscular injection-mediated immunological priming in dLNs often suffers from low vaccination efficacy due to unsatisfied initial infiltration of tissue-resident APCs and subsequent activation of dLN-resident immune cells [3, 12].
To trigger potent adaptive immune responses, sustained-release devices, use of nanovaccines (NVs), and enhancement of targeting ability have been developed to promote the recruitment of tissue-resident immune cells, the cellular uptake of antigens by APCs, and the delivery of vaccines to dLNs [10, 13–15]. Nevertheless, the effectiveness of conventional vaccinations that solely generate single-niche immunological priming either in the injection site or dLNs remains suboptimal. Novel immunization strategies are thus highly desirable, particularly with respect to emerging threats of rapid spread highly lethal infectious diseases [16].
Acupuncture, or acupoint stimulation, has long been used for alleviating various types of diseases, including chronic pain [17], hypertension [18], stroke rehabilitation [19], rheumatoid arthritis [20], diabetes [21], and others. Acupoints are specific body regions locating either on the skin surface or underneath.
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Lu Wang, Yanhong Sun, Meiling Yan, Lihua Wang, Yiyang Wang, Mengmeng Zhang, Qian Li, Huangan Wu, Jinyao Liu, Chunhai Fan (2025). Eliciting Dual-Niche Immunological Priming by Acupoint Delivery of Nanovaccines. Nano-Micro Letters. https://doi.org/10.1007/s40820-025-01789-y
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Frequently Asked Questions
What is acupoint delivery of nanovaccines (ADN)?
ADN is a novel immunization strategy that delivers nanovaccines at acupoints, simultaneously stimulating mast cell-assisted dendritic cell maturation at the acupoint and directly enriching nanovaccines into draining lymph nodes, thereby eliciting dual-niche immunological priming.
How does ADN enhance immune responses?
ADN enhances immune responses by provoking antigen presentation by lymph node-resident CD8α+ dendritic cells and inducing nanovaccine accumulation in B-cell zones, which amplifies cytotoxic T lymphocyte responses and immunoglobulin G antibody expression in draining lymph nodes.
What are the advantages of ADN over conventional vaccination?
ADN provides dual-niche immunological priming, overcoming the limitations of single-niche priming in conventional injections. It improves antigen delivery to lymph nodes and activates both T and B cell responses, leading to stronger and more durable immunity.
What potential applications does ADN have?
ADN has potential applications in tumor therapy and infection prevention, as demonstrated by effective antitumor responses and high-level antiviral antibodies in mice.
What is the significance of the dual-niche priming concept?
The dual-niche priming concept is significant because it addresses the inefficiency of conventional vaccines that only target one immune niche. By simultaneously engaging both the injection site and draining lymph nodes, ADN maximizes antigen presentation and immune activation, offering a more potent vaccination platform.
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