Journal of Vaccine Research 2024, Vol.14, No.5, 243-254 http://medscipublisher.com/index.php/jvr 245 biomolecules, making them suitable for delivering antigens and adjuvants. Their ability to enhance the presentation of antigens to immune cells and induce robust immune responses has been demonstrated in several studies (Curley and Putnam, 2022). Silica nanoparticles are another promising class of inorganic nanoparticles used in vaccine development. Their porous structure allows for high loading capacity of antigens and adjuvants, and their surface can be easily modified to improve biocompatibility and targeting (Zhao et al., 2014). Iron oxide nanoparticles, on the other hand, offer the added advantage of being used as contrast agents in magnetic resonance imaging (MRI), providing a dual function of vaccine delivery and diagnostic imaging (Curley and Putnam, 2022). However, the use of inorganic nanoparticles in vaccines also presents challenges, including potential toxicity, long-term biocompatibility, and the need for extensive safety evaluations (Zhao et al., 2014; Curley and Putnam, 2022). 3 Mechanisms of Action of Nanoparticle Vaccines 3.1 Antigen presentation and immune activation Nanoparticle vaccines enhance antigen presentation and immune activation through several mechanisms. One key mechanism is the efficient delivery of antigens to antigen-presenting cells (APCs) such as dendritic cells (DCs) and macrophages. For instance, guanidinylated cationic nanoparticles have been shown to encapsulate antigens and facilitate their uptake by DCs, leading to enhanced antigen presentation and subsequent immune activation. These nanoparticles stimulate the maturation of DCs and increase the production of cytokines, which are crucial for initiating and sustaining immune responses. Additionally, nanoparticles can promote antigen cross-presentation, a process where exogenous antigens are presented on MHC class I molecules, thereby activating CD8+ T cells and inducing robust cellular immune responses (Li et al., 2016). Another example is the use of aminated β-glucan and CpG-oligodeoxynucleotides (CpG-OND) in nanoparticle formulations. These nanoparticles target and activate specific receptors on APCs, such as dectin-1 and Toll-like receptor 9 (TLR9), enhancing antigen uptake and processing. This dual targeting approach significantly boosts both humoral and cellular immune responses, comparable to traditional adjuvants like Freund's adjuvant but with reduced toxicity (Jin et al., 2018). The ability of nanoparticles to enhance antigen presentation and immune activation is a critical factor in their effectiveness as vaccine platforms. 3.2 Targeted delivery Targeted delivery is another crucial mechanism by which nanoparticle vaccines enhance immune responses. Nanoparticles can be engineered to target specific tissues or cells, improving the localization and concentration of antigens at the desired site (Xuan, 2024). For example, ultra-small nanoparticles (25 nm) have been shown to efficiently enter lymphatic capillaries and target lymph node-residing dendritic cells via interstitial flow. This targeted delivery ensures that a significant proportion of the antigen reaches the lymph nodes, where immune responses are initiated (Reddy et al., 2007). In contrast, larger nanoparticles (100 nm) are less efficient in targeting lymph nodes, highlighting the importance of nanoparticle size in targeted delivery. Moreover, nanoparticles can be designed to exploit natural transport mechanisms within the body. For instance, nanoparticles coated with polyethylenimine (PEI) can enhance the uptake of antigens by macrophages and promote their migration to draining lymph nodes. This targeted delivery not only improves antigen presentation but also prolongs the duration of antigen exposure, leading to more sustained immune responses (Gu et al., 2019). The ability to precisely target and deliver antigens to specific immune cells or tissues is a significant advantage of nanoparticle vaccines. 3.3 Adjuvant effects Nanoparticles also exhibit adjuvant effects, which are essential for enhancing the immunogenicity of vaccines. These effects can be attributed to the inherent properties of the nanoparticles themselves or the incorporation of additional immunostimulatory molecules. For example, nanoparticles made of biodegradable materials such as poly(lactic-co-glycolic acid) (PLGA) can act as adjuvants by promoting the activation of dendritic cells and the production of pro-inflammatory cytokines (Silva et al., 2013). This activation is crucial for the initiation of adaptive immune responses.
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