Keywords

4.1 Introduction

Infectious diseases are the most significant cause of morbidity and mortality worldwide; pathogenic bacteria are responsible for approximately 50% of this burden. Vaccine development has a proud history as one of the most public health interventions to date.

A vaccine is a live killed, attenuated, inactivated form of pathogenic microbes like as bacterium or virus, or a part of the structure of the pathogenic microbe, that upon administration enhancing antibody production, i.e., cellular immunity against that but is incapable of causing severe infection. A vaccine should be cost-effective to preventing infectious disease, epidemiologically targeted implementation of vaccines has diminished morbidity and mortality from infectious diseases that earlier were causing problems and economic impediment, i.e., diphtheria, measles, polio, pneumococcal infections, and invasive Haemophilus influenza type B. Worldwide vaccination programs as per the guidance of WHO have eradicated smallpox diphtheria, poliomyelitis and the neonatal Tetanus in most of the developed and various developing countries (World Health Organisation 2019).

Vaccine development is moving in the direction of the rational design of new candidate vaccines that may no longer contain live or inactivated whole pathogens. In the delivery of the drugs field, the Nanotechnology has come out as an immense prospective technology to deliver at an appropriate define site. Based on these techniques, the needed drugs, proteins, nucleotides, and vaccines could be delivered more appropriately and to reach the specific targeted site (Mamo and Poland 2012).

Nanotechnology is the new interdisciplinary area to lead the predictable progress in molecular biology, biotechnology, diagnostics, and therapeutics. It gives way for the delivery of antigens, diagnosis of diseases, nanoemulsion etc. (Fig. 4.1) (Storni et al. 2005; Vijayakumar et al. 2011).

Fig. 4.1
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Schematic representation of various Nanoparticle Delivery systems [Virus Like Particle, Liposome, ISCOM, Polymeric Nanoparticle and Non-Degradable Nanoparticle]

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4.2 Nanovaccines

Nanoscales technologies are in medicine having more than four decades of age, i.e., Liposomes are nanoparticles with Phospholipids bilayer have been used in the pharmaceutical industry ever since in 1960 (Torchilin 2005). At present, the composition, size, charge, shape, hydrophobicity, and surface property of nano vaccines are undependable and that have been accepted for human use, and now the clinical/pre-clinical numbers are increasing.

The positive approach of nano vaccines, which is not only allowing antigen improvement as well as vaccine stability, immunogenicity, and pertained to discharging delivery of target. Currently, more numbers of prophylactic nano vaccines have been approved for human use, and some of the vaccines are in the phases of clinical/pre-clinical, due to the developments in Nanovaccinology (Kushnir et al. 2012; Plummer and Manchester 2011; Roldao et al. 2010).

In nanotechnology, an additional wide-ranging field is Nanovaccine is the newer technology of vaccination through the target spot of antigen delivery. The Mucosal immune response has more significance in the prevention of infection/spreading of disease, Encapsulation of antigen in suitable animal models with microparticles/nanoparticles is competent in enhancing the immune response.

The PLGA was loaded with Tetramethyl rhodamine-labeled dextran which is a hydrophilic polysaccharide used for microscopic analysis, was prepared by solvent evaporation methods and the resulted materials was administrated to a group of immunopotentiators like Macrophage and dendritic cells, after 24 h the microscopic results revealed that both immune cells are up taking same intensity. A number of nanosize formulated subunit peptide vaccine delivery strategies based on the composition of polymers, peptides, lipids, and inorganic materials have been proposed, and it was inducing a cellular and humoral immune response (Skwarczynski and Toth 2011). As per the research work of Tsai et al., the nano-vaccine bound with the T cell-stimulating molecules and the type 1 diabetes in mice was cured by a nanotech-based vaccine through the boost of the weaker immune cells to prevent from damaging (Tsai et al. 2010).

The nano-vaccines are target-oriented, and it consisted of biocompatible/biodegradable nanoparticle and its emerging field as a novel vaccine; it can able to directly target the disease/origin of infection that were different from the existing drug molecule those which affect all parts of the body. Nanovaccines have the reassurance together the entire body immune system to destroy infections and also prevent further infections as well as spreading of the diseases, and it can able to elicit cell and humoral immunogenicity. When compared with the DNA based available vaccine, and it is more reasonable than conventional vaccination. Modified adenovirus it contains self-assembled bio-nanoparticles that can able to deliver to the target gene, the immune response is elicited through the cells undergone translation progression for the secretion of the specific protein, the next type of nano-vaccine are, the needed synthesized polysaccharide molecules as a nanoparticle vaccine it can able to targeting the protein molecules and attached with a carbohydrate-binding domain that is special protein module. This methodology only permits the nanometer of the nanoparticles measuring between 50 and 90 nm, and the lesser size is required for the elicit immune primary immune response also decrease the time duration for the propagation of vaccine strains from 60 to 28 days (Pati et al. 2018).

4.2.1 Characterization of Nano Vaccines

To meet the required quality attributes the nanoformulation has to essential to undergone the characterization, i.e., structurally, composition, stability, etc. During the nanoformulation, more chances of dissimilarity occur due to contamination, poly dispersion of Nanoparticles, the accrual of toxic components or due to completion of particle formation to avoid that kind of variation either between or within advanced techniques are available to determine the identification of uniformity within the colloidal solution. Spatial distribution results are much needed in the nanoformulation for identification of antigen is encapsulated/conjugated on to the surface, surface modified and charge influences cellular uptake consequently the size may vary (minimum 20–200 nm maximum 2000 nm) based on the cellular specificity and migration towards the target region and shape of particles determine that the intracellular interaction and antigen-presenting capacity and enhance the immunity (Gao et al. 2018).

The following analytical methods are available for the characterization of Nanoparticles i.e., Electron microscopy [FESEM, SEM, and TEM], Dynamic Light Scattering [DLS, Zeta sizer, Zeta potential], and Density Gradient centrifugation (Caputo et al. 2019).

Hydrophobicity of NPs plays a significant role in the nano-vaccination in the interaction of antigen permeability to intracellular transport and solubilization of protein antigen. The techniques used for the presence/quantification/analysis of needed antigens are Lowry and Bradford assays, ELISA, Dot-blots assay, SDS-PAGE and Western Blot, Density gradient centrifugation.

In some occasion it may be necessary to measure the compositional content of the NP, the QuilA is very significant constituent for ISCOMs, the lesser concentration leads to a hemolytic effect, this deficit can be analysed through Reversed-phase HPLC/and the assay of Rocket Electrophoresis (Kersten and Crommelin 1995).

It is because some reagents lead to toxic when it is a high dose. The concentrations of Phospholipids and Cholesterol are significant components of ISCOMs; these are quantified through GC and Phosphorus assays (Lendemans et al. 2005).

Using with Inductively Coupled Plasma Mass Spectrometry/instrumental Neutron Activation analysis, the metal like gold was a presence in Nanoparticles (Fabricius et al. 2014).

4.3 Nanoparticle Interaction with Antigen-Presenting Cells (APC)

The immune cells like macrophage and dendritic cells have excellent facilities in uptake mechanisms with nanoparticles, and it leads to the development of essential and efficacious nanoparticle vaccines. The dimension, charge, and shape of the nanoparticles play a significant role in the antigen up taking as well the shape of nanoparticle are more stringent for the interaction with antigen-presenting cells (Dobrovolskaia and McNeil 2007; Kumari and Yadav 2011; Zolnik et al. 2010).

Studies of the antigen-presenting cells (APC) with nanoparticles of antigenic components have more attracted, broad significance with a focus on how the antigen to deliver in APC and further induction through cross-presentation and maturation of the Nanoparticle antigen towards the activation of cell-mediated and humoral immune response of CD4 and CD8 stimulated and production of specific antibodies (Babensee 2008; Bachmann and Jennings 2010; Gheibi Hayat and Darroudi 2019; Jones 2008; Reddy et al. 2006; Scheerlinck and Greenwood 2008)

4.4 Liposomes as Vaccine Delivery Vehicles

The Liposome concept was first investigated in the year 1965 (Bangham 2005). It has a structure of spherical lipid bilayer with core rings and aqueous. The diameter sizes are varying from micrometer to nanometre, and as a model for membrane transport through diffusion, at that moment the liposome is checked for the adjuvanticity and using for the different vaccine formulations due to its the biochemical molecules, the predominant of phospholipids in the aqueous core (Hall et al. 2004). The core and phospholipids are amphiphilic in nature, and it includes the tail are in hydrophobic nature, and it consisted of fatty acids are linked to a backbone of glycerol as a head group is a hydrophilic nature. Whilst as aqueous environment condition the polarized structure makes possible of self-assembly into behavior with the fatty acids facing each other due to this the oil like comportment forming among outwards facing phosphate groups, because of this the liposome’s are having both charges it leads to adaptable and important towards the antigen carrying. The antigen molecules like proteins/hydrophobic peptides when placed in into liposomal inner hydrophobic center the entire hydrophilic molecules are encapsulated in the vesicles or surface bonding can also happen (de Jonge et al. 2004; Glück et al. 1999; Han et al. 1997; Tiwari et al. 2011).

The antigen will bind in liposome through covalent attachment or electrostatic interactions along with few hydrophobic interactions. The advantages pertaining to liposomes is, it can highly adapt with the properties like physicochemical size, charge, and lamellarity to fine-tune of the liposomes through the altering of lipid composition (Szoka Jr and Papahadjopoulos 1980). As per the studies of Watson et al. (2012) and Giddam et al. (2012) the Liposome’s are non-toxic, non-immunogenic and biodegradable, and otherwise, if the composition is derivatives of bacteria or viral membrane that could enhance the immune response (Giddam et al. 2012; Hall et al. 2004; Li et al. 2011; Watson et al. 2012).

4.4.1 Antigen Localization in Liposomal Formulations

There are various ways to integrate antigens into liposomes before administration optimization of liposome as per its enhancement of immune response. While the liposome-encapsulated antigen immune response deficient due to unreachable of the antigen with APC, however when oral administration of the encapsulated antigen leads to enhanced stimulation of local IgA and serum IgG (Fujii et al. 1993; Phillips et al. 1996).

Consequently, the liposome formulation possibly customized for specific requirements and purposes. When the oral route administration of the vaccine can be easily enzymatic degradation, if the same vaccine is in liposome encapsulation, there is not possible of enzymatic degradation. As per the research finding of Wilschut et al. (1994), the immune response was enhanced while the liposomes are administrated before the administration of antigen (Wilschut et al. 1994). Fully encapsulated antigen immune responses are more than surface bounded antigens of liposome’s vesicle (Aramaki et al. 1994). The liposome-mediated immune response not only the selection of antigen and lipid composition, but it depends on the virtual magnitude and liposomal localization. This category of inventive methods way to the improvements of potential mucosal immune response based vaccines. The liposomal based vaccine has the additional adjuvant capacity will confirm to be a mucosal vaccine against different infectious diseases. The encapsulated and surface bounded antigenicity of liposomal are triggering the capacity of T and B cell priming (Moon et al. 2011).

4.5 Nanoemulsion

The nanoemulsion is the newer concept in vaccine delivery methods. In Michigan, university research groups have trailed the nanoemulsion in the size of 400 nm containing Hepatitis B antigen and the immune response are in the satisfactory levels (Fig. 4.2). During their research they are prepared the nanoemulsion with the soybean oil as oil phase along with alcohol, detergents, and water, the macro emulsion was further treated in ultra Sonicator in optimal temperature and other related parameters reduced to the size of the particles 400 nm, the nanoemulsion was entrapped with infectious antigen and placed in the nose for triggering the immune response instead of needle-based immunization and the immune response (Bielinska et al. 2008).

Fig. 4.2
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Transition of nanoemulsion

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The vascular endothelium, in various internal organs, is played a vital role for the allocation of nanoparticles, the critical parameters of the nanoparticles like charge, shape, size zeta potential, hydrophobicity are highly influenced with plasma protein, immune cells (Makidon et al. 2008; Sharma et al. 2009). The antigen is not degraded during permeation in the layers of skin and muscle due to protection of the nanoemulsion. Dendritic cells are located in the skin that also as the functioning of antigen-presenting cells, and it is the capacity of most competent migratory capacity, optimum efficiency towards capture and processing of MHC high-level expression, and also exclusion and co-stimulatory. Targeted delivery of protein antigen to dendritic cells was achieved (Banchereau and Steinman 1998; Cruz et al. 2011; Reddy et al. 2006).

4.6 Transdermal Immunization

Transdermal immunization is an innovative approach by which the antigen along with an adjuvant is applied directly on the skin that elicits potent humoral as well as cell-mediated immune responses specific for antigen (Glenn et al. 1999; Mishra et al. 2013; Peachman et al. 2009; Scharton-Kersten et al. 1999). It can significantly assist transdermal macromolecule delivery across intact skin. It generates an ephemeral opening in the skin barrier, enabling macromolecule to reach the systemic circulation. Advantages of transdermal immunization are: (1) it can interact the antigen directly to the antigen-presenting cells those were present in the skin; (2) reduced amount of antigens required for the immunization; (3) sustained release; (4) reduce the frequency of administration; (5) patient compliance; (6) self-administration is possible; (7) eliminate accidental needle-stick; (8) non-invasive zero-order delivery; (9) reduce the overall cost of immunization (Hammond et al. 2000).

For Transdermal immunization, various techniques are available like Iontophoresis, Sonophoresis, Microneedle delivery (Fig. 4.3) to enhance the immunization safe, pain-free, and affordable price. Enhancement of nanoparticles and chemical enhancements are being explored for the Jet injection route of vaccination. The available vaccine is conventional that is lacking in the accurate adjuvants; there is a scope to find suitable, safe, affordable, and effective adjuvants that are most needed in modern vaccinology. To concern with that, the transdermal based immunization has been analyzed by the research and development community. Stratum corneum lies in the layer of skin, and it is densely associated with the antigen-presenting cells (APC), the APC are mainly dendritic and Langerhans cells in the epidermis and dermis region (Kim et al. 2012).

Fig. 4.3
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Transdermal delivery pathway techniques

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During the Transdermal immunization, first, the strategic targeting to epidermis and dermis, without disrupting the underlying subcutaneous tissue, is a complicated technique that requires only those who are professionally trained healthcare personnel. The microneedle techniques have been a proposal of suitable/potential replace of that skin disrupting issue as well as existing hypodermic syringes.

4.7 Microneedles

The skin is firm because of the stratum corneum, the microneedles are solid and the theory of “punch with the piece,” the MNs are only in the size of a micrometer. It has the suitable/needed drug or antigen are any nanoformulations are directly pierced through the skin barrier [stratum corneum] in a suitable direction that is horizontal to the smooth of the skin (Fig. 4.4) (Kim et al. 2012).

Fig. 4.4
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Microneedle

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Because of the micron size, the MNs drug/vaccine tube permitted the material through the skin and no needs of professional training, currently, the existing vaccine injection, that persons/should be professionally trained. In addition, the MNs are pain-free, now the self administrable MNs patches contained an assortment of appropriate vaccine coated that make possible extensive distribution of the vaccine/drug inappropriate and short time of the uncontrolled disease. Dry coated microneedle vaccine formulation in the immunobiological industry will restrict the cold chain cost as well as distribution to remote areas in developing countries. The microneedle based vaccine has dose-sparing quality in which targeting the immune cell productive zones, there are four major types of microneedles in development: solid, coated, dissolving, and hollow microneedles. The microneedle patch vaccine formulations in the pharmaceutical industry will minimize the laydown cost of cold chain processes and improve the distribution of vaccines to rural areas located in developing countries (Arya and Prausnitz 2016).

However, the dose sparing quality is one more extensive improvement MNs whither, the explicit targeting of affluent convolutions of immunogenic APCs, there the production of high immunogenicity than the traditional IM route. Currently, lots of research analyses are being organized globally to collectively correlate the efficient immunogenicity induced by MNs immunization as contrary to existing routes of delivery. The studies of Dean et al. (2005) in the Rabies vaccine, the rabies vaccine was injected through 1–3 mm BD Soluvia microneedle syringes to 66 healthy volunteers towards the confirmation of safety and consistency. During immunization using only one-fourth dosage of rabies vaccine, the seroconversion rate of the volunteers has a higher range, than the IM route, in the same time the quantity of the antigen was very lesser (one fourth) and this study clearly indicated that targeting the immune cells, that contains more numbers of immune cell networks (Dean et al. 2005).

The reactions of the small hollow implantable dissolving-type microneedle that formulated with freeze-dried hepatitis B surface antigen along with aluminum hydroxide and lipopolysaccharide as adjuvants, which derived comparable immune responses as the liquid formulation of the vaccine after two immunizations (Hirschberg et al. 2010). The various researchers stated in their reports that affluent stimulation of virus-specific memory B cells and enriched lung clearance in Mice than IM delivery of inactivated seasonal influenza virus vaccines coated on solid metal microneedles indicated that the microneedles hold an encouraging possible as an alternative to conventional vaccine administration methods (Kim et al. 2009, 2010a, b, c; Koutsonanos et al. 2011).

During the coating and drying process, there is a possibility of aggregation of antigen particles to overcome through the addition of trehalose as a stabilizer was added in inactivated influenza virus strain A/PR/8/34 vaccine for stability quantification analysis (Quan et al. 2009). The same virus strain was used for the analysis of its immunogenicity, the virus coated metal MNs was inoculated in Mice and found strong Th1 but not in IM routed vaccine (Kim et al. 2010c). Moreover, Kommareddy et al. (2012) focused on H1N1 research, and further, they fabricated dissolving-type microneedles encapsulated antigen of inactivated influenza and used for immunization in mice and the immunogenicity are allowable in the standard limit (Kommareddy et al. 2012).

A liquefy microneedle patch abide of the biocompatible polymer poly vinyl pyrrolidone and encapsulated with inactivated influenza virus strain A/PR/8/34 vaccines, and it induced robust antibody responses and enhanced cellular immune responses than intramuscular route immunization (Quan et al. 2009). The dose sparing techniques of MNs in pre-clinical assessment of whole inactivated influenza virus vaccine in the laboratory animals of mice affirms that 100-fold dose sparing when the same was administrated through Intradermal route (Alarcon et al. 2007). Detailed studies were also done in MNs that were coated with rotavirus vaccine formulation, and the immunogenicity was in acceptable range (Moon et al. 2013).

The influenza vaccine MNs in mice, they inferred that increasing concentration of cytokines that earlier immune response and the cytokines play an important role in the functioning of dendritic cells, macrophages, and neutrophils (del Pilar Martin et al. 2012). Analysis of low-dose microneedle and low-dose intramuscular routes of the same antigen, the other critical parameters are in same, after the scheduled duration the animals are bleed and the elicited immune response, and that the low-dose microneedle persuaded higher immune responses that were comparable to the serological antibody titers produced by high-dose intramuscular route (Quan et al. 2010a, b).

4.8 Virus-Like Particles

The virus-like particles are molecules closes as a virus, and it is a collection of self-assembling multi-protein molecules like viral structural proteins, i.e., capsid, envelope, and due to non-availability of viral genetic material, there is no possibility of replication. The outer surface of VLPs serves as immunogenic epitopes, and that elicit strong B and T cell response. Gardasil et al. developed the commercially approved HPV composed with L1 VLP are shown highest virus-neutralizing antibody titers in the laboratory animal [C57BL/6], the L1VLP HPV vaccine was delivered to mice through Microprojection–Nanopatch a densely packed array and the booster with IM route (Corbett et al. 2010).

The influenza virus strain H1N1 A/PR/8/34, the HA subunit along with matrix protein [M1] with the VLP, the formulated VLP vaccine shown higher immune response (Kim et al. 2010c). The VLP vaccine formulated with the sugar glass stabilizer [trehalose] the immune response of the trehalose based VLP influenza have more antibody titer when compare with the without, as well as the stability also more. In the case of the microneedle delivery, the VLP H1N1 with trehalose, the antigen is not destabilization, the immune response was more when compared with conventional IM route of immunization (Kim et al. 2010b; Quan et al. 2009). During the virus challenge method for potency analysis, the VLP H1N1 with HA subunit were coated in microneedle and applied to mice skin through manual, after the elicited the immune response all the mouse is survived that means both conventional IM routes are identical (Song et al. 2010a, b). The H1 (A/PR/8/34) and H5 (A/Vietnam/1203/04) VLP, and they found that the microneedles in human skin shown more morphological changes and cell number in epidermal sheets of Langerhans cells (Pearton et al. 2010).

In addition, a mechanism study examining the effect of microneedles in human skin presented a line of evidence indicating that H1 (A/PR/8/34) and H5 (A/Vietnam/1203/04) VLP vaccines delivered by microneedles stimulated Langerhans cells, which resulted in cell morphology change and a curtailed cell number in epidermal sheets (Pearton et al. 2010). The VLPs are now commercially available; it is self-assembled targeted viral protein, as well as it as an antigen delivery platform (Ionescu et al. 2006; Tissot et al. 2010) Garg et al. (2020), reported that, VLP based vaccine for Zikha virus [ZIKV VLP] after challenged in the small animal model and found that the generated high titer of neutralizing antibodies. The VLP based vaccines are in the trail as well as various phases, the diseases like Chikungunya and Japanese encephalitis and Dengue virus, CHIKV has shown more efficacy in animal model now it is under clinical trial, in case of JEV and DENV the VLP are utilized with prME expression without capsid protein (Akahata et al. 2010; Garg et al. 2020; Wong et al. 2019).

4.9 Advantages of Nanovaccine

The currently available major nano-vaccine is non-invasive, and the route of delivering are oral, nasal, diffusion patch or microneedle array, these techniques are more advantage, i.e., pain-free, multi-dose and needle-based The nanoemulsion preparation of Hepatitis B antigen found to be tolerable and effective and does not require refrigeration and it is effective for a month at 25 °C and for 6 weeks at 40 °C; therefore it facilitates its final distribution in small areas/villages of developing countries (Nandedkar 2009; Vijayakumar et al. 2013).

Currently nano-vaccine against HIV gp120, it is the most important binding protein, and it induces the cellular and mucosal immunity, the immune response of the HIV gp120 is above the acceptable range. The peptide-nano-bead based nano-vaccine against FMDV, influenza, more encouraging results.

4.9.1 Potential Issues with Nanovaccine

Any new medicine is needed their considerable evidence regarding the safety, efficacy, and potency is mandatory prior to small trails with the beginning of human trails, the important worries with nano-vaccine technologies are (1) Biocompatibility with host system; (2) Toxicity variations; (3) Nanoparticle size, charge and shape not in composition; (4) Issues in toxicity, while long term accumulation in vital internal organs; (5) Lacking reproducibility in large scale; and (6) Small nanoparticles are cleared quickly from the body (Luo et al. 2017).

The evaluation of nanoparticles is very tough while during the rapid selection of nanoformulations for vaccine/drugs; the nanoparticles lead to adverse effects on humans are likely exposure (low level) from the long term, which is more complicated and also needs very prolong testing for identification.

The facility towards designing nanomaterials is needed to regulatory guidelines for protecting the safety of nanomaterials in universal and nanomedicines in particular. Undoubtedly it is mandatory to characterize the nanomaterials expected for therapeutic use in both it is manufactured qualities initially and after induced into physiological surroundings (Lin et al. 2014).

4.10 Conclusion

In the coming few decades, Nanotechnology will have a significant impact on all phases of an existing medicine. The application of nanotechnology in vaccines will create them more productive and fewer invasive and may provide opportunities to develop new vaccines against unpreventable, incurable diseases. Perhaps most importantly, nanotechnology will allow vaccine formulation which is stable enough to be distributed without refrigeration to remote villages in the developing world, where access to medical facilities is minimal, it could save many lives, and slow the spread of HIV, malaria, and other major infectious diseases. Many of the nano vaccines are non-invasive, delivered by the oral or nasal route, diffusion patches, or microneedle arrays, thus allowing pain-free delivery with minimal damage. This is an advantage over conventional vaccines, which are usually multi-injection, multi-dose delivery systems (Kendall 2006).

In the research finding of the biodegradable nanoparticles have enormous possible as transport carriers for mucosal and systemic vaccine delivery system. Generally, the concentric fatty sphere produced by the virus, and it elicits a powerful immune response nanoparticle-based vaccine (Akagi and Akashi 2006).

When the nanoemulsion based vaccine is available in the market, there is not necessary of refrigeration/cold storage for a month at 25 °C, and for 6 weeks at 40 °C and these are applicable in developing countries during the final allocation in remote villages/areas. The MHC based peptide nano vaccines against autoimmune disease with massive potential (Clemente-Casares et al. 2011). The observation of Zhang et al. (2006) observed that when the nanomaterials were stored in long-duration, there are changes in the particle size and shape but not in composition and it leads to toxicity due to the clearance of the particles, hence further the proper evaluation of the nano-vaccine in the aspects of safety, efficacy, and potency (Zhang et al. 2006).

The Nanoparticles delivery systems have been more advantages when compared with the conventional vaccine. The conventional vaccine antigens are poor immunogenicity it needed a proper adjuvant to enhance the immunogenicity, at the same time as in aluminum-based adjuvants have been used, while in immune response there is a shortage as well as reactogenic with the host during immunization, this kind of reactogenic, shortfall of immune response will be alternated with nano-vaccine with the various delivery system. This is not only the delivery of antigen but also host biocompatibility along with the superior immune response (Akagi and Akashi 2006).

One of the ways in which NPs are capable of eliciting different immune responses is through their size; moving into cells passing through the non-classical pathways and then processed as such, delivering antigens in different ways also has a retrospective effect on the resulting immune response, whether the antigen is decorated on the NP surface for presentation to antigen-presenting cells/encapsulated for slow release and prolonged exposure to the immune system. The NPs are also adaptable and can be customized with immunostimulatory compounds to improve the potency of the immune response or with molecules to increase their stability in vivo. While these delivery vehicles may present as an exciting prospect for future vaccination strategies, it is also worth noting their potential drawbacks, particularly those associated with cytotoxicity (Gao et al. 2018).

Ever since the Nanovaccines have only short narration, and it not have a long-standing safety profile used for human use. Further, it needs more studies to be carried for toxicity; once this happens as expected, this may be the improved alternative technique for the vaccine delivery and further licensed for human use. Nanovaccine based on biomimetic principle consists of distinct impacts like biocompatibility, low toxicity, bioavailability, and targetability undergo as an outstanding agent to cure various diseases (Vijayan et al. 2019).

The upcoming triumph of vaccine shall not only depend on the achievement of scientific advancement, but it needs the association of researchers from interdisciplinary in diverted fields such as physical chemistry, structural biology, epidemiology, bioinformatics and molecular immunology, the success of vaccine will be accomplished through inventive ideas that will lead the basic breakthrough The phenomenal scientific consideration among the technological improvement of in the discipline of immunology collectively with nanomaterials is the key contributor to vaccine advancement (Kim et al. 2019).