Nanoparticles – Enabling Innovation in Vaccine Design

Vaccines are an important tool to fight diseases. Despite recent ground-breaking successes in vaccine development, there remains an unmet need for vaccines to treat numerous deadly conditions such as tuberculosis and HIV. Conventional vaccines (live-attenuated pathogens and inactivated pathogens) and subunit vaccines, though widely used, come with challenges such as limited immunogenicity and reversion to pathogenic virulence. Innovative strategies to tackle these challenges can open a new era of vaccine technology.

Nanoparticle-based vaccines have emerged as a potential alternative to conventional and subunit vaccines. This article explores the various properties and advantages of nanoparticles which allow the design of vaccines with enhanced antigen presentation and strong immunogenicity. 

Nanoparticles-based vaccines – Understanding the basics

Nanotechnology involves the fabrication and manipulation of matter at the nanoscale, between 1-100 nm, approximately. Nanoparticles-based vaccines are arguably the next generation of vaccine technology as they offer numerous advantages compared to traditional approaches, largely because of their size: nanoparticles and viruses operate at the same length scale. Mariusz Skwarczynski, senior researcher at the University of Queensland, says, “All the SARS vaccines that are commercialized are indeed nanoparticles, all of them. The viral vector or virus itself is a naturally occurring nanoparticle. Because of this size similarity with virus, nanoparticles are readily identified by the immune system.”

Nanoparticle-based vaccines can be developed by attaching viral antigens on the nanoparticle surface, "decorating" them. Attachment of the antigen to the nanoparticle surface enables the presentation of the viral antigen to the body’s immune system in nearly the same way that it would be presented by an invading pathogen. Another method is encapsulating the vaccine components within the core of the nanoparticles, which allows for the safe delivery of the antigen as it is protected from degradation.

Nanoparticles, acting as adjuvants, can increase the antigenicity of the attached antigens, and are able to mimic the virus and thus act as antigens themselves. Nanoparticles can induce innate and adaptive immune responses. Nirmal Marasini, post-doctorate research fellow at the Woolcock Institute of Medical Research explains, “Nanomaterials enhance the immunogenicity of the vaccines by preserving their integrity during their risky journey to target immune cells. They enhance antigen recognition by the immune cells, provide additional danger signals and evoke the desired immune responses against [the] administered antigens.” 

The highly specific surface area and nanoscale size associated with nanoparticles make them suitable for utilization as antigen carriers, ultimately enhancing antigen processing and presentation. These properties enable the controlled release of antigens and efficient cell targeting.

Accelerating the Study of Viral Infection and Therapeutics

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Designing nanoparticles for vaccines

Advances in material science have enabled the design of nanoparticle vaccines with remarkable physicochemical properties. The size, surface chemistry, shape, solubility and hydrophilicity of nanoparticles can be adjusted and regulated to prepare vaccines with the desired biological properties. Of these properties, size is particularly important, as it determines the ability of the nanoparticle to induce an immune response. The size of the particle also impacts the cellular uptake mechanism. 

The pharmacokinetic parameters, release rate, biodegradability and biocompatibility depend on the composition of the nanoparticles. Based on their components, nanoparticles can be classified as organic or inorganic. Organic nanoparticles include polymeric micelles, virus-like particles, liposomes, dendrimers and carbon nanomaterials. Organic nanoparticles are biocompatible, biodegradable and nontoxic. Gold nanoparticles, metal oxide and mesoporous silica nanoparticles are inorganic nanoparticles. Compared to organic nanoparticles, inorganic nanoparticles possess improved stability, enhanced permeability and enable high drug loadings and a triggered release profile. 

How can the use of nanoparticles improve vaccine efficacy?

The use of nanomaterials as a platform technology can help manufacturers improve vaccine efficacy. Skwarczynski explains, “Nanoparticles are preferentially taken up by antigen-presenting cells (APCs), the cells that are responsible for recognizing pathogen invasion (or vaccine presence) and activating immune responses. APC uptake is size driven – usually smaller nanoparticles are more easily taken up and therefore trigger a stronger immune response. Larger nano/microparticles can form a depot effect, in other words, the antigen (particles) stays at the injection site where it is slowly released into the surrounding area (mimicking local infection).”

Nanoparticles protect the encapsulated antigen from enzymatic degradation. “Even if presented on the surface of the nanoparticle, the dense packing of antigen on the nanoparticle surface blocks easy access by enzymes,” says Skwarczynski. In addition, small nanoparticle vaccines can readily access the lymphatic system and reach the lymph nodes, which are important centers of immune responses.

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Nanoparticles in oral vaccine development

Oral vaccines are able to induce immune responses at the mucosal level, which is the first site of infection for several pathogens, in addition to triggering systemic immune responses. These factors, combined with the increased patient compliance associated with oral vaccines, make them an attractive option when compared to needle-based vaccines. However, their successful development is challenging. Marasini explains, “The major challenge in the development of oral vaccines is ensuring their stability in the hostile environment of the gastrointestinal tract (acidic pH of stomach and presence of proteolytic enzymes). Effective transportation of vaccines across the intestinal membrane remains an equally challenging issue.” 

Nanoparticles, due to their distinct properties, are seen as a viable solution to such challenges. “Vaccines, when incorporated into nanoparticles, enhance the stability of vaccines against gastrointestinal degradation and efficiently translocate across the intestinal membrane. They are then available to the immune cells for further processing,” Marasini adds.

Entering a bright future with nanotechnology

With their unique properties, nanoparticle vaccines are set to offer novel opportunities for improving vaccine efficacy; however, challenges remain. There is a need for high throughput manufacturing methods and scale-up techniques. The challenge of heterogeneity, which propagates through manufacturing processes, can increase the cost of quality control. Technology transfer from the laboratory to the market is also a challenge that will need to be overcome.