[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.
1.4.2 Inorganic Nanoparticles
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 SiO2-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].
1.4.3 Biomolecular Nanoparticles
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.
1.4.4 Liposome
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].
1.4.5 Virus-Like Particles
Another biomolecular NPs known as VLP has a typical virus shape but lacks viral genome, rendering them inactive and unable of replication. They quickly and effectively produce a strong and prolong immunological response in the host [79]. Hepatitis B protection is provided first with a VLP-based human vaccination[80]. VLPs have recently been used as vehicles for several human papillomavirus (HPV) vaccines. According to a recent study, HPV vaccinations based on VLPs elicit a strong cross-protective antibody response [81]. During chronic infection, cytotoxic T cells are essential for removing damaged cells and regulating microbe load. They can really be highly effective in vaccines because they target the T-cell response.
1.4.6 Micelles
The cores of micelles, another type of biomolecular NPs, are hydrophobic in contrast to liposomes and VLPs [82]. They are widely used with weakly water-soluble drugs delivery or encapsulated amphiphilic compounds [83]. Micelles have been used in two different ways as vaccine delivery systems. First, protein vaccines may be simply covalently attached to the hydrophilic micelle. HIV vaccines have been attached to adjuvant-loaded micelles using this approach, resulting in significant APC activation in vitro [84]. Model peptide antigens coupled to polymer-lipid microspheres are demonstrated to attach protein albumin and travel to the lymphatic vessels, where they significantly raise T-cell numbers and act as an anticancer vaccination [85]. Endosome disruption can be triggered by polymer-based micelles, allowing vaccines to be transported to the cytoplasm, resulting in significant cytotoxic T-cell responses [86]. Molecules with similar or identical hydrophobic moieties can also be self-assembled and form heterogeneous micelles. This phenomenon has been utilized to create protein amphiphile microspheres capable of transporting several antigens to the same cell [87].
1.4.7 Immunostimulating Complexes
ISCOMs are biomolecular structures. They are made up of cholesterols, phospholipids, and Quil A saponins. ISCOMs have an immunostimulatory effect because they contain Quil A saponins, which are well-known adjuvants. ISCOMs have been studied for around 35 years to be highly effective as a synthetic vaccine [88]. Still, they can cause significant, unfavorable injection-site reactions [89], limiting their use to animal vaccinations [90]. ISCOMA-TRIX is identical to the traditional ISCOM except that the Quil A saponins are first filtered to give a specified group of saponins that do not induce substantial inflammation [91]. ISCOMA-TRIX has been demonstrated to produce immune responses in mice and rabbits [92].
1.4.8 Self-Assembled Proteins (SAPNs)
SAPNs are 20–30 nm icosahedrons. For the manufacture of NPs-based vaccinations,
