Applications of Nanoparticles in Vaccine Delivery
Traditional vaccines can be divided into four types: live attenuated vaccines, inactivated vaccines, subunit vaccines, recombinant vaccines, polysaccharide and conjugate vaccines, and toxoid vaccines. While many of these vaccines play an important role in controlling infectious diseases, some vaccines do not provide good protection against the disease, and there are no licensed vaccines for many infectious diseases. Moreover, there are also security issues that bother us. For example, it is dangerous to use some live vaccines in immunocompromised populations in society. Recombinant or polysaccharide vaccines are safer, more defined, and less reactive than many existing vaccines, but are generally inferior immunogens. That's why we need adjuvants to enhance their efficacy. Aluminum-based adjuvants are the most commonly used adjuvants, but there is a limitation: they may induce local reactions and not produce robust cell-mediated immunity. As a result, scientists are focusing more on developing novel adjuvants and delivery systems for next-generation vaccines.
Nanoparticles (NPs) are a new type of vaccine delivery vehicle with good application prospects. Vaccine antigens can be encapsulated into NPs or coupled to NP surfaces (Fig. 1). Therefore, NPs are ideal for the delivery of antigens that degrade rapidly upon injection or can induce a transient local immune response. In addition, NPs made of certain composite materials can not only perform site-specific delivery of antigens but also prolong the release time of antigens.
Figure 1: Schematic diagram of nanocarrier structure
So far, many biodegradable or biocompatible NPs have shown great promise in improving antigen-specific immune responses, such as polymer particles, chitosan, gold or silver particles, and magnetic particles. These The characteristics of NPs and their use in vaccine formulations are discussed below. Polymer Particles Polymeric particles are used to encapsulate antigens, helping to prevent antigen degradation and control the sustained release of antigens. Polylactic-glycolic acid (PLGA), poly-D-lactide (PLA), and poly ortho-ester (POE) are the most widely used polymer particles with particle sizes over 200 nm. These particles are biodegradable or biocompatible and have been approved for use in humans. Although polymer particles are capable of encapsulating large-sized drugs and improving uptake and targeting by coupling to suitable functional groups, they also suffer from antigen stability issues during encapsulation, storage, and release.
Chitosan Nanoparticles
Chitosan is a linear polysaccharide extracted from chitin extracted from crustacean shells. Due to their polycationic, biodegradability, biocompatibility, adhesiveness, and ease of physical and chemical modification, they have been used as drug delivery matrices. Chitosan can be easily linked with other polymers, including polyethylene glycol (PEG), tripolyphosphate (TPP), or PLGA, to form chitosan nanoparticles for enhanced protein or antigen loading. Due to its natural positive charge, chitosan easily encapsulates negatively charged DNA, making chitosan also ideal for DNA vaccine delivery. Furthermore, its inherent adhesiveness facilitates the transport of peptides and proteins across mucosal barriers, providing advantages for antigen delivery via oral and nasal routes.
Biocompatible Nanoparticles
Latex, gold, silica, or polystyrene particles are nondegradable but biocompatible and have been used successfully as antigen carriers and adjuvants. Antigens conjugated with these particles can induce long-term immune reactivity because these particles are present in tissues and provide an antigen reservoir for persistent stimulation. The study showed that although the polystyrene nanoparticles were gradually cleared from the lungs, they were still detectable a month after infusion. In addition, gold nanoparticles can enhance the efficiency of DNA vaccination by promoting Th1 and Th2 responses. At the same time, silica nanoparticles are also used as gene-delivery vehicles in basic research and clinical trials.
Magnetic Nanoparticles
As a promising drug, magnetic nanoparticles have been used in many biomedical applications, such as magnetic resonance imaging, targeted drug delivery, and vaccine vectors. These particles have different forms including spherical, rod, hollow, and core-shell. Recently, scientists synthesized superparamagnetic iron oxide nanoparticles /polyethyleneimine (SPIONs/PEI) polymer complexes in vitro to enhance the aggregation and delivery of a malaria DNA vaccine (MSP1-19) in eukaryotic cells. The results showed that the expression of MSP1-19 was significantly increased under the external magnetic field (Figure 2). Furthermore, the cytotoxicity of the complex was comparable to the benchmark non-viral agent Lipofectamine 2000.
Figure 2: Densitometry results of PyMSP1-19 produced by SPIONs/PEI-A/DNA polymers with or without magnetic field and Lipofectamine 2000 reagent during gene transfection. Experiments were performed in at least three replicates.
Although a wide variety of nanoparticles have been developed and used as delivery vehicles or immune enhancers, nanoparticles in vaccine delivery are still in the early stages of development. Many challenges remain: 1) it is difficult to reproducibly synthesize non-aggregated nanoparticles with consistent and desirable properties; 2) we still lack a fundamental understanding of how the physical properties of nanoparticles affect their biodistribution and targeting; 3) we should be more to better understand how these properties affect their interactions with biological systems, from the cellular level to tissues and throughout the body. By solving these problems, novel vaccine systems based on nanoparticles will become more practical in the near future.
References
1. Gregory, A. E., Williamson, D., & Titball, R. (2013). Vaccine delivery using nanoparticles. Frontiers in cellular and infection microbiology, 3, 13. https://doi.org/10.3389/fcimb.2013.00013
2. Al-Deen, F. N., Ho, J., Selomulya, C., Ma, C., & Coppel, R. (2011). Superparamagnetic nanoparticles for effective delivery of malaria DNA vaccine. Langmuir, 27(7), 3703-3712. https://doi.org/10.1021/la104479c
3.Pati, R., Shevtsov, M., & Sonawane, A. (2018). Nanoparticle vaccines against infectious diseases. Frontiers in immunology, 9. https://doi.org/10.3389/fimmu.2018.02224
4. Zhao, L., Seth, A., Wibowo, N., Zhao, C. X., Mitter, N., Yu, C., & Middelberg, A. P. (2014). Nanoparticle vaccines. Vaccine, 32(3), 327-337. https://doi.org/10.1016/j.vaccine.2013.11.069
5.Sahdev, P., Ochyl, L. J., & Moon, J. J. (2014). Biomaterials for nanoparticle vaccine delivery systems. Pharmaceutical research, 31(10), 2563-2582. https://link.springer.com/article/10.1007/s11095-014-1419-y
6. Xiang, S. D., Fuchsberger, M., De L. Karlson, T., Hardy, C. L., Selomulya, C., & Plebanski, M. (2013). Nanoparticles, immunomodulation, and vaccine delivery. In Handbook of Immunological Properties of Engineered Nanomaterials (pp. 449-475). https://doi.org/10.1142/9789814390262_0015