Micro and Nanoparticle‐Based Delivery Systems for Vaccine Immunotherapy: An Immunological and Materials Perspective

Abstract

The development and widespread application of vaccines has been one of the most significant achievements of modern medicine. Vaccines have not only been instrumental in controlling and even eliminating life-threatening diseases like polio, measles, diphtheria, etc., but have also been immensely powerful in enhancing the worldwide outlook of public health over the past century. Despite these successes, there are still many complex disorders (e.g., cancer, HIV, and other emerging infectious diseases) for which effective preventative or therapeutic vaccines have been difficult to develop. This failure can be attributed primarily to our inability to precisely control and modulate the highly complex immune memory response, specifically the cellular response. Dominated by B and T cell maturation and function, the cellular response is primarily initiated by potent immunostimulators and antigens. Efficient and targeted delivery of these immunomodulatory and immunostimulatory molecules to appropriate cells is key to successful development of next generation vaccine formulations. Over the past decade, particulate carriers have emerged as an attractive means for enhancing the delivery efficacy and potency of vaccines and associated immunomodulatory molecules. Specifically, polymer-based micro and nanoparticles are being extensively studied for a wide variety of applications. In this review, we discuss the immunological fundamentals for developing effective vaccines and how materials and material properties can be exploited to improve these therapies. Particular emphasis is given to polymer-based particles and how the route of administration of particulate systems affects the phenotype and robustness of an immune response. Comparison of various strategies and recent advancements in the field are discussed along with insights into current limitations and future directions.

Subcutaneous inverse vaccination with PLGA particles loaded with a MOG peptide and IL-10 decreases the severity of experimental autoimmune encephalomyelitis

“…Because the induction and maintenance of immune tolerance is influenced by the persistence of the antigen and can be supported by tolerogenic cytokines, the use of biodegradable micro-nanoparticles is ideal for inverse vaccination because they can support a sustained release of several entrapped molecules [23].…”

“…PLGA allows for the fine-tuning of the degradation rate and subsequent antigen release from several days to more than one year by modulating the polymer lactide-glycolide ratio, the molecular weight, and the crystal profile [22]. The controlled and/or sustained release of antigens and immune modulators from polymeric materials has been used previously to induce the proper immune effector response [23]. The use of PLGA-NP can enhance tolerance induction in some delivery settings, such as nasal vaccination [24].…”

Nanoparticle conjugation of CpG enhances adjuvancy for cellular immunity and memory recall at low dose

“…Induction of long-lasting CTLs with subunit vaccines requires, first, delivery of antigen to cross-presenting dendritic cells (DCs) and, second, potent activation of these DCs by the vaccine adjuvant, which instructs DCs how to activate T cells. Nanocarriers can be used to modulate the immune response induced by antigens and adjuvants by modifying their characteristics, such as stability, tissue and cell targeting, and DC-activating capacity (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). We have previously described the targeting benefits of conjugating antigens to ultrasmall Pluronic-stabilized poly(propylene sulfide) (PPS) nanoparticles (NPs) in terms of CD8 + T-cell and Th1 responses (13,14).…”

Engineered PRINT® nanoparticles for controlled delivery of antigens and immunostimulants

“…Incorporation of cationic components into PRINT particles allows the adsorption of negatively charged nucleic acid, polysaccharide, and protein antigens to the particle surface. 6,18 This strategy allows encapsulation of antigens and adjuvants in the particle matrix as well as use of particle surface to deliver complex mixes of antigens and immunodulators to cells. In addition, positively charged nanoparticles are taken up by cells more easily due to the negative charge of the cells.…”

“…In addition, positively charged nanoparticles are taken up by cells more easily due to the negative charge of the cells. 18 Careful consideration of particle size, shape, surface charge, and antigenic composition allows for the development of particles that more closely resemble native pathogenic viruses and bacteria in contrast to subunit vaccines. The ability to produce vaccines that better mimic pathogenic targets in a multifaceted way provides the opportunity to advance the field of vaccinology beyond subunit-based and live attenuated vaccines.…”