Nanoparticle-based vaccines exhibit a wide range of advantageous physicochemical properties that can aid in the targeted delivery of novel vaccines while simultaneously improving their efficacy.

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Introduction

As of late September 2020, the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was responsible for the death of over one million people worldwide. In 2016, before SARS-CoV-2 emerged, the World Health Organization (WHO) reported that approximately 3.2 million deaths were directly caused by lower respiratory infections, 1.4 million of which were due to tuberculosis (TB) alone.

Taken together, these millions of deaths that are caused by both new and old infectious diseases have substantial impacts on the global socioeconomic and healthcare sectors.

An overview of vaccine types

Since many of these infectious diseases are difficult to treat, the ultimate goal to combat their spread and deadliness is to develop effective vaccines. An ideal vaccine for any disease is one that is safe, stable, and capable of eliciting a long-lasting immune response with a minimum number of doses.

Although many of the vaccines that are widely distributed are attenuated or killed whole organisms, several other types of vaccines have shown promising results in their immunogenic profiles. Subunit vaccines, which are also referred to as second-generation vaccines, as well as third degeneration vaccines which can be RNA- or DNA-based, are some of the leading candidates in novel vaccines.

While many of these alternative vaccine approaches have been shown to elicit protective immunity against several different diseases, they are associated with certain challenges that limit their effectiveness in a clinical setting. DNA and RNA vaccines, for example, are cost-effective and associated with minimal infection risks but can be easily degraded as a result of delivery challenges to target sites.

Protein-based vaccines, which have already been successfully used for the immunization against various infectious diseases ranging from acellular pertussis and tetanus to diphtheria and pneumococcus, often require adjuvants, which can be associated with their limitations, to enhance their immunogenicity.

NPs boost vaccine immunity

Various types of NPs are associated with inherent physical properties that can activate an immune response. Gold, carbon, dendrimers, polymers, and liposome NPs have all been found to induce cytokine and antibody responses. These unique characteristics have therefore expanded the potential utility of NPs from delivery vehicles for vaccines to adjuvants that can enhance the immunogenicity of vaccine candidates.

NPs that are used for this purpose are otherwise known as nano-immuno activators or stimulators and are typically within the size range of 20 to 100 nanometers (nm). Some examples of known nano-immuno stimulators include inorganic NPs like iron and silica, polymeric NPs including chitosan and poly(lactic-co-glycolic) acid (PLGA), cholesterol and lipid liposomes, as well as VLPs.

After PLGA NPs, liposomes are the second most common type of NP to be employed for clinical applications in the form of both vaccine and drug delivery vehicles. Liposomes are composed of lipids that have a hydrophilic head and a hydrophobic tail that self-assemble in water under certain conditions.

Depending upon the charge, size, and specific lipids that comprise a given liposome formulation, this category of NPs are capable of inducing cellular and/or humoral responses. The administration of PEGylated liposomes, for example, has been shown to elicit a response by immunoglobulin M (IgM) molecules in an in vivo model.

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NPs for vaccine delivery

As compared to conventional vaccine approaches, nano carrier-based delivery systems offer several advantages including enhanced protection against premature degradation, good stability, and improved adjuvant qualities. When used to encapsulate or coat the surface of an antigen, nanocarriers can protect the immunogen from premature proteolytic degradation, thereby allowing researchers to explore alternate routes of administration.

In addition to their protective qualities, nanocarriers can also improve the specificity of antigen delivery to APCs and increase the duration of antigen presentation to these cells and other important immune cells needed to achieve long-term immunity.

A large variety of nanoparticles (NPs) have been evaluated as potential antigen carriers for vaccine purposes, some of which include inorganic and polymeric NPs, virus-like particles (VLPs), liposomes, and self-assembled protein NPs. Gold, carbon, and silica NPs are all biocompatible inorganic NPs that have been successfully used to deliver viral antigens.

Gold NPs have shown particular success in the delivery of both viral and bacterial antigens as a result of their ability to induce robust host immune responses. Gold NPs in vaccines have been used in vivo against influenza, the human immunodeficiency virus (HIV), foot and mouth disease, and tuberculosis. Gold NPs, as well as other inorganic NPs like silica, are low cost, highly reproducible, and associated with good safety profiles, all of which make these NPs highly advantageous for vaccine development processes.

Aside from their immunogenic potential alone, liposomes can also deliver vaccines by fusing with the target cell membrane. Liposomes are highly versatile in that the aqueous core of these molecules allows for hydrophilic molecules to easily get incorporated within this type of NP, whereas hydrophobic substances can feasibly be encapsulated within their phospholipid bilayer.

Some of the different types of liposomes that have been included in NP-based vaccine studies include both unilamellar and multilamellar vesicles comprised of biodegradable phospholipids such as phosphatidylserine, phosphatidylcholine, and cholesterol.

References and Further Reading

• Pati, R., Shevtsov, M., & Sonawane, A. (2018). Nanoparticle Vaccines Against Infectious Diseases. Frontiers in Immunology 9. doi:10.3389/fimmu.2018.02224.
• Diez-Arevalo, D., & Zeng, M. (2020). Nanoparticle-based vaccines. Nanopharmaceuticals; 135-150. doi:10.1016/B978-0-12-817778-5.00007-5.
• Al-Halifa, S., Gauthier, L., Arpin, D., et al. (2019). Nanoparticle-Based Vaccines Against Respiratory Viruses. Frontiers in Immunology. doi:10.3389/fimmu.2019.00022.

Written by

Benedette Cuffari

After completing her Bachelor of Science in Toxicology with two minors in Spanish and Chemistry in 2016, Benedette continued her studies to complete her Master of Science in Toxicology in May of 2018.During graduate school, Benedette investigated the dermatotoxicity of mechlorethamine and bendamustine, which are two nitrogen mustard alkylating agents that are currently used in anticancer therapy.