Nanovaccinology as Targeted Therapeutics

Figure 1.2 Antigens are delivered to antigen-presenting cells (APCs) using surface-engineered NPs. Reproduced (adapted) from [30]. Copyright 2018, Frontiers.

Liposomes, NPs having a phospholipid bilayer, have been used in the pharmaceutical industry since 1960 [31]. NPs have a diameter of 1 to 100 nm ( Figure 1.3), whereas antigens or DNA segments have 1 to 10 nm [32]. Therefore, they are susceptible to being absorbed by biological systems, and it is the first step in eliciting immunogenicity. A nanovaccine is composed of NPs and can be composed of protein, lipid, metals, polymers, and other materials. The positive strategy of nanovaccines allows for not only antigen enhancement but also vaccine stability, immunogenicity, and effective target delivery. Due to advancements in nanovaccinology, many nanovaccines have already been licensed for clinical use, and others are in clinical trials [33–35]. Adjuvants and multiepitope antigens may be effectively co-delivered into target cells and APCs using nanovaccines, and the release of antigen in the cytoplasm and antigen cross-presentation can be precisely controlled.

Figure 1.3 The size comparison of various biological systems used in nanovaccinology. Reproduced (adapted) from [36]. Copyright 2016, IntechOpen.

Polymeric NPs can be made by polymerizing monomeric units or by using synthesized polymers. The customizable qualities, size, composition, and surface properties of these NPs make them appealing in the medical industry because they allow for regulated release and drug molecule protection [37]. Poly (lactic acid) (PLA), poly (glutamic acid) (PGA), PLGA, and chitosan are the most frequently used polymeric NPs for vaccine formulation [19]. The chemical structure of polymeric NPs is designed to behave differently in different environments to control the release rate. The function and uses of other polymeric NPs vary substantially depending on the inherent chemical and biological effects in distinct materials [38]. PLGA is a biodegradable and biocompatible polymer that can undergo in vivo hydrolysis [39] and encapsulate and release different biomolecules over time [40–42]. Under physiological conditions, these NPs may incorporate antigens and inhibit their destruction for one month, which is crucial for vaccination [43]. Furthermore, PLGA NPs promote antigen processing and display to susceptible cells by promoting antigen uptake by APCs [44]. Other NPs, chitosan, and N -(2-hydroxypropyl)methacrylamide/ N -isopropyl acrylamide were also investigated as vaccines preparation [45–47]. Chitosan is a favorable and promising polymer for DNA vaccine formulation because of its cationic character, which allows attachment to the DNA, generating DNA–polymer interactions that protect DNA from enzyme hydrolysis. It is indeed extremely hydrophobic, inactive, and non-immunogenic, with bio adhesive properties that facilitate mucosal vaccination techniques. Chitosan has been further discovered to have natural adjuvant properties, stimulating dendritic cell maturation to enhance T helper 1 (Th1) responses [48]. Over the years, multiple developments have resulted from chitosan-based NPs delivery technology, including a therapeutic potential anti-tumor papillomavirus (HPV) vaccine [49], treatment methods for influenza A [50], highly contagious myocarditis [51], and some livestock diseases such as Newcastle disease (ND) virus [52, 53] and Noda virus [54]. Polymeric NPs have biocompatibility, antigen encapsulation and stability, regulated release of antigens, cellular retention in APCs, microbe characteristics, and delivery feasibility [55–57]. As the research advancements of polymer science continue, vaccine technologies will develop accordingly.

Inorganic NPs have sparked a lot of interest in vaccine formulation because of their simplicity in drug loading and bioactivity properties. Furthermore, their thermochemical stability makes sterilization easier [58]. Inorganic materials are relatively nontoxic and can be manufactured in a variety of sizes, forms, and dimensions. Gold (Au) NPs are a popular inorganic nanomaterial used in vaccine delivery because of decreasing toxicity, increasing immunogenic activity, and providing vaccine storage stability [59]. Another extensively investigated composition for vaccine delivery is carbon NPs [60] which has good biocompatibility [61, 62]. Protein and peptide antigens can be coupled on CNTs for delivery, which has increased IgG response levels [62–65]. Mesoporous carbon NPs have been studied for use as an adjuvant in vaccinations [62]. Silica is another promising material for nanovaccinology because of its biocompatibility and having excellent properties as nanocarriers. Silica NPs’ size and form can be altered selectively to regulate their cellular interaction [66]. Many silanol groups on surface are advantageous for introducing additional functionalities, such as cell recognition, biomolecule absorption, improved cell contact, and cellular uptake [67–69]. It is revealed that DNA vaccine incorporated into SiO 2-layered double hydroxide induces antibody response as well as boosts T-cell multiplication and pushes T helper (Th1) cells toward Th1 activation [70]. Superparamagnetic iron oxide NPs (SPIONs) is another inorganic material for nanovaccinology. SPION-based vaccine delivery system is modified to improve the stability of vector and APC targeting ability to ensure prolonged exposure in the target area [71]. Other nanomaterials have been used as vaccine delivery vectors and adjuvants, including silver (Ag) NPs and calcium phosphate NPs [71, 72].

The biomolecular materials have a number of advantages that make them attractive candidates for synthetic vaccine preparation. They are biologically inspired systems that are built on the basis of biomolecules. Biomolecular materials benefit from transporting a range of carriers and displaying diverse moieties on their surfaces [19]. Although a number of biomolecular NPs have been investigated, liposomes, virus-like particles (VLPs), micelles, and immunestimulating complexes (ISCOMs) ( Figure 1.4) are the four most widely used materials for vaccine applications [60].

Figure 1.4 A schematic illustration of various NPs that have been used as vaccinations [60]. Reproduced (adapted) from [60]. Copyright 2013, Frontiers.

Liposomes are sphere NPs comprised of lipid layers [73] which are formed when lipids with a hydrophilic part and a hydrophobic part combine in water. Liposomes can encapsulate a variety of medications and be utilized for regulated delivery for their substantial therapeutic uses [74]. There has been a lot of research done on liposomes and their vaccine potential. Liposomes have the advantage of being able to be modified to obtain desired immunostimulatory effects. A unique nanovaccine system targets inflammatory cells and increases innate immunity to T cells against a mimic antigen created by modifying liposomes to have lectin binding mannose on their surface and trapping monophosphoryl lipid A (MPLA) adjuvant [75]. While liposomes have been used to administer vaccines against various infections, one particularly intriguing application is tuberculosis prophylaxis, a fatal disease [76]. Virosomes have been used in clinical trials for a number of preventive purposes, including tetanus and hepatitis B vaccinations [77]. It is recently shown that virosomal immunizations could be programmed to selectively activate T lymphocytes, improving immunization protection against influenza infection [78].