A Pervasive Review On New Advancements of Nano Vaccines On Covid-19 Pandemic

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A Pervasive Review on New Advancements of Nano Vaccines on Covid-19

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Article in International Journal of Pharmaceutical Sciences Review and Research · October 2021
DOI: 10.47583/ijpsrr.2021.v70i02.015
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Int. J. Pharm. Sci. Rev. Res., 70(2), September - October 2021; Article No. 15, Pages: 126-143 ISSN 0976 – 044X
Review Article
A Pervasive Review on New Advancements of Nano Vaccines on Covid-19 Pandamic
Ranajit Nath1*, Ambika Mandal1, Ratul Bhowmik2, Ratna Roy1, Riya Biswas3, Soubhik Bhattacharyya1
1* NSHM Knowledge Campus, Kolkata- Group of Institutions, Kolkata, West Bengal, India.
2Department of Pharmaceutical Chemistry, SPER, Jamia Hamdard, New Delhi, India.
5Jadavpur University, Department of Pharmaceutical Technology, West Bengal, India.
*Corresponding author’s E-mail: [email protected]
Received: 18-07-2021; Revised: 23-09-2021; Accepted: 30-09-2021; Published on: 15-10-2021.

ABSTRACT
The infection that causes COVID-19 may be a pathogen referred to as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-
2) and is believed to possess originated from China's Wuhan Province. The rapid spread of coronavirus disease 2019 (COVID-19) has
become a worldwide concern, with the planet Health Organization (WHO) declaring it an epidemic on March, 2020. To enter the cells,
SARS-CoV-2 S requires angiotensin-converting enzyme 2 (ACE2). Many existing vaccines have drawbacks like insufficient system
stimulation, in vivo instability, high toxicity, the need for a chilly chain, and multiple administration. A nanotechnology is an efficient
tool for addressing these issues. A successful vaccine against SARS-CoV-2 infection is predicted to stimulate innate and adaptive
immune responses and protects against severe sorts of coronavirus disease 2019 (COVID-19). Different strategies are introduced
because the go after an efficient and safe vaccination has begun. Currently, the foremost common vaccine types studied in clinical
trials include viral vector-based vaccinations, genetic vaccines, attenuated vaccines, and protein-based vaccines. during this review,
we cover the foremost promising anti-COVID-19 vaccine clinical trials also as various vaccination strategies to shed more light on the
continued clinical trials. it's also discussed how nanotechnology is often wont to better understand the pathology of the present
pandemic, also as how our understanding of SARS-CoV-2 cellular uptake and toxicity can influence future nanotoxicological
considerations and nanomedicine design of safe yet effective nanomaterials.
Keywords: Nano vaccine, COVID 19, strategies, clinical trial, drawbacks.
The three months from the date of 30th January 2020,

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when the first COVID-19 case was recorded officially in
India, we have found that there were over thousand and
DOI: thousand deaths happened from that disease, which is
10.47583/ijpsrr.2021.v70i02.015 now across 537 in the rest of South Asia. In this pandemic
situation, India logged a huge amount of COVID-19 deaths
DOI link: http://dx.doi.org/10.47583/ijpsrr.2021.v70i02.015
than Ireland. Statistically found that from May 10, 2020,
India had passed 2,000 death cases and therefore India
was starting lockdown restrictions because it touched up
INTRODUCTION to 180,000 death cases by the middle of June. 1
T he novel coronavirus which is now officially declared

as severe acute respiratory syndrome coronavirus 2
or SARS-CoV-2, is considered to be the main
causative agent of that COVID-19 disease. The Wuhan city
which is located in China was the first epicenter of this
The direct transmission mode of this virus is happening via
(1) aerosols, which is formed via dental procedures and
surgical procedures or it can be transmitted in the form of
respiratory droplet; (2) mother to her child (3) human
secretions and discharge and body fluids, for example,
disease, but now more than 8.3 million cases have been urine, feces, semen, tears, and saliva. This virus is most
reported. The particular word “coronavirus” is given commonly spread via respiratory droplets which formed
because the club-shaped protein spikes are present on while sneezing, talking, coughing of an infected person to
their upper surface when viewed under a special type of other normal people. The risk of transmission will increase
microscope which is known as transmission electron if a virus-infected person is present within a 1-meter
microscope (TEM). According to the genetic information, diameter of another person. On the other way, Indirect
the virus is divided into four categories Alpha, Beta, transmission occurs via (1) surfaces of furniture and
Gamma, and Delta 26 of which the main causative agent fixtures present within the immediate using environment
behind all the COVID-19 pandemic situations belongs to of infected patients and (2) objects which are used by the
the beta class 9. infected person. 24
Two types of regional epidemics are a middle east Epidemiological study shows that the symptoms of this
respiratory syndrome known as MERS and a severe acute disease are cough, fever, dyspnoea, accounting for 82%,
respiratory syndrome known as SARS in 2012 to 2015 and 83%, and 31% of the COVID-19 patients respectively.
2001 to 2003, respectively. 6
International Journal of Pharmaceutical Sciences Review and Research
Available online at www.globalresearchonline.net 126
©Copyright protected. Unauthorised republication, reproduction, distribution, dissemination and copying of this document in whole or in part is strictly prohibited.
Generally, the incubation period in COVID-19 is quick, it one N-terminal ectodomain, and one C-terminal
may vary from 5–6 days or 2–11 days in co-vid infections.21 endodomain, which helps in defining the shape of the
virion 26.
The main symptoms of covid-19 patients are fatigue, chills,
fever, loss of appetite and protracted cough in the lungs, (iii) the E protein is called an envelope. it is the smallest
etc. Some features of infection of SARS-CoV-2 are anosmia, protein among them and plays a very important structural
loss of smell, and loss of taste, these symptoms are found role, it helps in assembly and budding in the virus. This E-
in approximately 64% of cases within the infected patients. protein is a short type of protein that comprises 76-109
When this viral infection spreads to the lower respiratory amino acids, because of its small size its ranging between
tract then it becomes a precursor of severe disease is 8.4 and 12 kDa. It also contains 40 loops and 35 α-helices.
unclear; then pneumonia with the characteristic of The protein contains a large part of hydrophobic
pulmonary ground-glass changes its opacity on the chest transmembrane made of 25 amino acids with a long c
CT scans. Some other features of severe disease are terminal domain and has a short length hydrophilic
respiratory compromise, renal damage, Blood clotting, and terminus containing 7–12 amino acids. The hydrophobic
cardiovascular collapse. 2 region helps in the gathering of viral genomic
information34.
Based on their genetic relationship, genetic information,
and genomic structures, this virus can be divided into four According to the cell entry mechanism of Coronavirus it is
genera. They are referred to as Alpha, Beta, Gamma, and attached to cellular attachment factors and bind with
Delta. Among the seven recognized human coronavirus specific cellular receptors such as angiotensin-converting
which is founded or reported, the HCoV-NL63 and the enzyme 2 (ACE2). this ACE2 receptor is mostly originating
HCoV-229E belong from the Alpha genera, and the other in the human epithelia of the lung and small intestine 17.
rest of the five types belong from Beta genera. 26
So, this virus attaches with ACE2 and host factors which are
Structure of corona virus the cell surface serine protease TMPRSS2, endorse the
fusion method by combined at the cellular membrane 46.
The basic structure of coronavirus is designed with long
RNA polymers which are tightly packed into the center part Previously known that the S protein or Spike has a
of the particle because it is a single-stranded RNA virus, receptor-binding domain (RBD) that intermediates direct
and then it is surrounded by a protective capsid. This interact with that cellular receptor such as angiotensin-
capsid has a lattice of repeated protein molecules, that’s converting enzyme 2 (ACE2) after binding with that cellular
why they are called capsid proteins or coats. These receptor the S1/S2 polybasic cleavage site is cleaved with
repeated proteins are called nucleocapsid (N). Then the the help of cellular cathepsin L and the host factor
core of the coronavirus particle is further surrounded by transmembrane protease serine 2 (TMPRSS2). So, after
another outer membrane envelope. This membrane that TMPRSS2 helps in the viral entry at the human plasma
envelope is made of lipids where proteins are inserted or membrane surface whereas in another site cathepsin L
embedded. The virus was last assembled in these also activates the Spikes in cellular endosomes and it
membranes which are derived from the cells, but they are compensates with the cell for the viral entry into cells that
modified to contain specific viral proteins, which are the are absent TMPRSS2 21.
spike (S), membrane (M), and envelope (E) proteins. 9
After that, the next step in the coronavirus lifecycle is the
First, (i) the S protein is also known as Spike glycoprotein translation of the replication of the gene from the viral
that helps in the attachment of the virus to host cells by gRNA. That viral replicase gene encodes two large ORFs,
membrane fusion method, so they encourage the entry of rep1a and rep1b. Two co-terminal polyproteins, one is
corona virus into the host cells. These S proteins are clove- pp1a and another one pp1ab are expressed by those ORFs,
shaped and are type-I transmembrane proteins. They have rep1a and rep1b. the replicase polyproteins cut by some
3 segments: one is a large ectodomain, another is a single- proteases, which are encoded by coronaviruses. To
pass transmembrane, and the last one is an intracellular produce an environment for promoting RNA synthesis by
tail. now the ectodomain part of the S proteins contains the replicase–transcriptase complex (RTC), this (RTC) is
the S1 subunit (which containing a receptor-binding created by the assembling of the NSPS. This procedure
domain also known as RBD), and the membrane-fusion S2 leads to RNA replication and transcription of the viral
subunit. 34 RNAs15.
Now, the S2 domain also has two heptad repeats (HR1 and Corona viruses can quickly replicate their viral gRNA to
HR2) and enriched alpha-helices, which are featured as create another RNA copy those are united into newly
typical fusion proteins 26. shaped fresh viral particles. Corona viruses have one of the
significantly large RNA genomes edged by 5′ and 3′
(ii) the abundant protein is called M protein (membrane).
untranslated regions. This particular RNA genome holds
the purpose of this protein is to maintain the membrane
cis-acting structures that help in RNA synthesis 46.
integrity of that virus 9.
When the viral RNA is entered into the human cytoplasm
The M protein is a small type of transmembrane protein
and translation started then ORF1a and ORF1ab produce
(25–30 kDa). they contain three transmembrane sections,
the pp1a polyprotein and pp1ab polyprotein. This leads to found. Not only by drugs but a vast range of vaccines are
producing 16 non-structural proteins by the viral proteases proposed against covid-19 17.
(encoded by ORF1a). after construction of the RNA
Testing for the Virus
replicase–transcriptase complex (RTC), this RTC produce
full-length (−) RNA copies, which then offer templates to Corona virus is a single strand RNA virus, and thus all
produce full-length (+) RNA genomes by the use of rough existing RNA detection is the best detecting method to
endoplasmic reticulum (ER)-derived membranes. Then detect this virus. so, the reverse transcriptase method can
after transcription, these RNA genomes also produce transcribe this viral genome into a DNA complement. the
another subset of sub-genomic RNAs. this viral RNA then ideal corona virus test is amplifying the DNA templates by
encoding all accessory and structural proteins for the viral PCR, and then proceed the other real-time versions of such
particle. In the end, all translated proteins and genomic tests 34.
RNA are collected into some envelope in the ER–Golgi
First, the test sample is submitted to CDC for testing then
intermediate compartment. At last, these envelopes are
the result is confirmed with a TaqMan real-time RT-PCR
later released by exocytosis 3.
assay. The requirement of this RT-PCR is three different
Conventional approaches to treat Covid-19 probe and primer sets. First collect multiple primers and
probe from the different sections of the corona virus viral
One of the most important drugs to treat covid-19 is
genome, which can be get from other human and animal
Hydroxychloroquine sulfate and chloroquine phosphate.
coronaviruses discriminately with a possible detection
these two drugs are anti-malaria drugs. In the mammalian
limit. The real-time RT-PCR assay is more complex than a
cell, culture studies show that they revealed to change in
conventional RT-PCR assay or culture isolation. So, it's the
the acidic conditions of organelles. They are very much
acceptable assay technique to detect covid during a clinical
used in inhibiting the terminal glycosylation of ACE2
sample 13.
against the corona virus, which leads to stop the fusion of
the corona virus with the cell membrane and stop the reverse transcriptase real-time PCR (RT-PCR) involves most
infection 17. of the testing to detect active COVID-19 infections, but
there are also different molecular technologies. Two
Not only it inhibits the glycosyl-transferases of the corona
different molecular technologies like loop-mediated
virus but also modifies the viral post-translational part of
isothermal amplification or CRISPR-mediated detection
some other viral families 37.
also uses in some cases, but the application of these tests
Hydroxychloroquine was a primarily effective solution to is often finished with previously developed tests that
covid infection, but the safety of the drug was stressed. already detect viral agents. rapid antigen detection tests
also use to detect the infection, but rapid antigen
Remdesivir is also an important drug, which acts as an
detection tests are less sensitive, and also less utilized as
inhibitor of the RNA-dependent, RNA polymerase. In vitro,
compared with RT-PCR. there are many drawbacks during
it shows the inhibitory activity against SARS and the MERS.
these methods, so RT-PCR is sort of the only method
For patients who have mild to moderately severe COVID-
among them 44.
19 infection and no need for respiratory support,
remdesivir cannot show significant benefit and its use is Why choose nano in the COVID -19 PANDEMIC?
not suggested by doctors. patients who have a high risk of
The idea of using nanotechnology is that viruses like
hyperinflammation and who need supplemental oxygen
COVID-19 work on a similar scale as nanomaterials.
and who are diagnosed in the initial stage in less than 10
Nanomedicine has emerged as a powerful platform that
days, redeliver is very useful for them because it shortens
has led to the development of novel materials and devices
the time to recovery of those patients and reduces the risk
with a wide range of applications, especially in imaging,
of further infection 28.
diagnostics, and therapy, which contributed to the early
If we compare between the Remdesivir and the detection and treatment of diseases. The promise of
Chloroquine, Remdesivir found post entry blockage of viral nanotechnology is lying in the potential of manipulating
infection with concentration at 50% of EC50=0.77 µM matter on the small scale used either by nature or by
whereas Chloroquine was showed with concentration at humans. This opens new vistas to work at the scale of the
50% of EC50=1.13 µM. Remdesivir Cytotoxic concentration cells and microbe-like viruses. 41
at 50% of CC50>100 µM and Chloroquine cytotoxic
Nanotechnology is defined as the development and use of
concentration at 50% of CC50>100 µM and an effective
materials and devices with at least one dimension of fewer
concentration at 90% EC90 of 6.90 µM. Chloroquine shows
than 100 nanometers. Nanomedicine is the application of
efficiency at entry or post-entry level, but remdesivir is
nanotechnology that involves the use of nanoparticles for
shown efficiency only post entry-level 37.
disease diagnosis, treatment, control, and prevention.
Similarly, favipiravir is moderately popular for covid-19. it Nanocarriers or nanoparticles are used to deliver drugs to
is also inhibiting RNA polymerase because it is a guanine target sites to deliver nano-therapeutic molecules or nano
analog. Generally, it is used for influenza treatment. After vaccines. 8
many clinical trials, the effectiveness against COVID-19 is

Nano-sensors are used for viral detection and monitoring. Nano vaccine
Nano-based viral receptor blockage:
Nanotechnology is popularly increasing as a strong device
▪ Inhibition of viral attachment by the use of Nano vaccine for solving these kinds of
infection, which are spreading from viruses because nano
▪ Inhibition of viral entry and infection
vaccines are new kind of vaccines are incorporated
▪ Host cell protection nanoparticles as carriers or adjuvants 19.
Nanotechnology could help the fight against COVID-19 This inert nanocarrier creates a strong shield after one
through different approaches, such as avoiding viral dose, that’s why they're very useful for various numbers
contamination and spray by 8 applications. because of the small size of nanoparticles, it
gets easy admission to tumors, which shows much
• Design of infection-safe personal protective
potential within the treatment of cancer therapy. Nano-
equipment (PPE) to enhance the safety of healthcare
sized particles also use for vaccine construction for the
workers and development of effective antiviral
treatment of varied viral agents 20.
disinfectants and surface coatings, which can
inactivate the virus and prevent its spread. Nano vaccines can encourage not only quick but also long-
lasting humoral and cellular protection. It is often
• Design of highly specific and sensitive nano-based
administered through multiple delivery routes so easily,
sensors to quickly identify the infection or
like oral, intravenous, intranasal, transdermal, etc. it can
immunological response.
also use to specialize in the crossing of the blood-brain
• Development of new drugs, with enhanced activity, barrier. the foremost mechanism of Nano vaccines is to
decreased toxicity, and sustained release, as well as clone the size and shape of pathogens to endorse easy
tissue target, for example - to the lungs. approval by immune cells. The nano vaccine is dependable
on nanoparticles, which successively depends upon the
• Development of a nano-based vaccination to boost particle shape, size, surface charge, and hydrophobicity, so
humoral and cellular immune responses. as that they're going to control and alter the self-
Conventional vaccines adjuvating effects, release kinetics, also controls multiple
delivery routes 31.
Conventional vaccines usually consist of disease-causing
pathogens or antigens that function by mimicking the In nano-vaccines the size of nano particle is that the
infectious agent to stimulate the host's immune response. foremost vital thing, it determines the internalization and
The pathogens can be modified as replicating or non- biodistribution and internalization. Particles that range
replicating agents, but in either case, the structure of cell between 20–100 nm size can penetrate directly into the
membranes or proteins of the pathogens remains intact to lymphatic system within a few hours from the time of
be able to interact with the immune system. 46 administration, but if the particle size is between 200–500
nm then it must be affected by antigen-presenting cells
A range of stimuli-responsive properties such as genetic, and reach late to the lymphatic system 2.
molecular, enzymatic, targeting, optical, or chemical could
be incorporated into nanomaterials, and nanomaterials Nanoparticles are very helpful as delivery systems because
can be engineered to have some of or all these properties it facilitates antigen uptake and processing by antigen-
in one single device. Those smart materials have the presenting cells. However, now a day’s scientists were
potential to provide highly active and specific therapies capable of decorating self-assembling protein
with minimal side effects and maximum therapeutic Nanoparticles (1c-SApNPs) with the spike’s protein of
outcome. 31 corona virus. These new Nano vaccines are great samples
of how can incorporate Nanotechnology and that enhance
Design materials to overcome the most common delivery the therapeutic effect of COVID-19 vaccines. Hence, an
obstacles, which are often associated with circulation time oral multi-modal NANO vaccine is often used for specific
and stability as well as tissue extravasation and cell targeted delivery into the tract by the use of a man-made
internalization. This will be essential to find viral particles mRNA, to increase the immunostimulatory activity of the
efficiently and target them for destruction by developing vaccine, so simply adding antibodies or some small
nano vaccines involved in host cell protection and immune molecules that might help in inhibiting the interaction
and immunity response and/or anti-viral nano agents, between ACE2 and corona virus. 11
involved in inhibiting viral attachment, cell entry, and
systemic infection. 21 Advantages of using nano vaccine 19
For the treatment COVID-19, vaccine applicants include ▪ Better stability in blood flow to increase the shelf life
different kinds of vaccines. they're inactivated vaccines, in the blood
live-attenuated vaccines, subunit vaccines, for virus-like ▪ Enhanced immune system stimulation
particles (VLPs), and last DNA and RNA vaccines. Nowadays
almost 16 vaccine candidates are tried for clinical ▪ No need for booster doses
testing35,45. ▪ No need to maintain the cold chain
▪ Ability to create active targeting Table 1: Characteristics of nanocarriers as nano vaccines 20

Nanoparticles can interact with immune machinery, Size Immune
Nanocarriers Source
inducing cellular and humoral immunological responses. (nm) response
Studies have shown that nanoparticles that range in size Humoral-
between 20 and 200 nm are preferentially internalized by Spore Bacterial Various
cellular
endocytosis into APCs (resulting in the T cell response),
Membrane Humoral-
while large particles (0.5-5µm) are usually internalized by Proteosome 20-80
protein-based cellular
phagocytosis (inducing the humoral immune response). 8
Exosome Cellular 50-100 Cellular
Vaccines using NP systems (NPb-Vs) can be delivered in
two ways: 53 Liposome Lipid based Various
Humoral-
cellular
1. Antigen or RNA/DNA is encapsulated in a nanocarrier.
Liposome +
Humoral-
2. Attaching antigens on the nanocarrier surface, to be Virosome viral envelope Various
cellular
exposed to the environment. proteins
Novel NPs can improve the performance in the treatment Biodegradable Humoral-
Super-fluid 25-250
polymer cellular
of respiratory diseases through different mechanisms of
action which are: 48 Inert Humoral-
Nanobead 40
nanomaterial cellular
(i) The development of polymers with faster mucus
Virus-like Humoral-
penetration and do not remain stuck, overcoming particles
Viral Various
cellular
this barrier
Humoral-
Phage Bacterial Various
(ii) The creation of biodegradable NPs with the stability cellular
to overcome the cell membrane and act in the lung
with minimal levels of toxicity, causing no lesions Acute respiratory distress syndromes (ARDS) are
during treatment distressing diseases characterized by severe pulmonary
inflammation and hypoxemic conditions, which can result
(iii) Modification of the chemical structure of NPs by in severe illness and death. The most important
adding surface capping agents such as polyethylene therapeutic approaches have been focused on a variety of
glycol (PEG) ways for effectively inhibiting severe inflammations or
Two types of vaccines based on nanoparticles: 43 managing the subsequent physiological imbalance, which
triggers respiratory lapse. 38
i) Self-assembly nanoparticles- representing modified
Adenoviruses. ARDS patients are now treated with a variety of treatment
approaches:
Delivers the target gene (cell generate protein needed to
trigger an immune response). ❖ Anti-inflammatory agents - corticosteroids,
pharmaconutrients, antioxidants, anti-proteases, and
ii) Synthesized polysaccharide nanoparticles- target ketoconazole
protein molecules.
❖ Ventilator agents - neuromuscular blockers, β2
Nanocarriers/NPs-based delivery system 8 agonists, and surfactants
▪ Protect nano vaccines from premature degradation ❖ Diuretics
▪ Increase stability ❖ Anti-coagulants
▪ Have excellent adjuvant properties ❖ Vasodilators a
▪ Help in the targeted/controlled delivery of ❖ Others.
immunogens to APCs (Antigen-presenting cells)
The general treatments for ARDS and blocking IL-6, IL-1,
Nanomedicine Approach for COVID-19 Therapeutics and TNF in cytokine storms may be useful for COVID-19-
(Rational Selection of Drug-Nanocarrier Combination) induced ARDS 8. Apart from these approaches, various
emerging therapies have also been reported, which
Nanocarriers can load and distribute a wide range of active include anti-inflammatory agents (statins, insulin,
moieties, including antivirals, biologics, and nucleic acids. macrolides, MMPs, aspirin, vitamin D, anti-interleukin 8),
The commercial success of nanomedicine against the cellular therapies (stem cells, growth factors, colony-
SARS-CoV-2 virus depends on connecting the right stimulating factors) angiotensin-converting enzyme (ACE)
therapeutic candidate to the right nanocarrier for a given inhibitors.
clinical state. Smart nanocarrier designs, such as the
prodrug strategy, are also required for the nano-delivery Additionally, there are some emerging treatments for
of biologics.[9] COVID-19, for example, 25,26

▪ Small-molecule drug-based therapies nanomaterial to induce complimenting immuno-

modulatory effects. The following section highlights the
▪ Immune regulation therapy, and interferon utilizing
rational design of nanocarrier-based vaccines with two
▪ NK cell therapy strategies
▪ Exosomes Antigen-Dependent Nanocarrier Selection
▪ Pluripotent stem cells (iPSCs) Loading antigens inside or on the surface of nanocarriers is
dependent on several factors including the antigen’s
Strategies for Nanomedicine Approach for COVID-19
physicochemical characteristics, biological stability, target
Therapeutics
sites, and required immunogen release rate. The physical
a. Nanocarrier Selection to Bypass the adsorption of antigens on nanoparticles is based on their
Conventional Limitations of a Drug Candidate surface charge and non-covalent hydrophobic
interactions. Antigens with an amphoteric nature are most
Nanocarriers are used to prevent the systemic
suitable for adsorption or surface immobilization on
immunotoxicity of protein-based drugs and promote
nanocarriers such as chitosan and dextran sulfate-based
immuno-oncology therapeutics. E.g. Lipid nanoparticles
polymeric nanoparticles, inorganic nanoparticles (such as
(LNPs), polymeric nanoparticles were developed with a
AuNPs), and carbon nanotubes. 9
high auristatin payload.
Antigen release in such cases is predesigned based on the
Chemically Alter/ (Re) engineer Drugs.
properties of the biological environment like pH, ionic
Drug molecules are altered to improve their compatibility strength, temperature, etc. Encapsulation and matrix
with a particular class or type of nanocarriers, rendering entrapment of the antigens within a nanocarrier is another
this a more generic approach for drug candidates with technique used to prevent its biological degradation. Poly
similar physicochemical properties. Use of cholesterol- (lactic-co-glycolic acid) (PLGA) nanoparticles are ideal for
modified hydroxychloroquine (Chol-HCQ) loaded encapsulating antigens and provide controlled or extended
liposomes that lowered the dose and toxicity of biological release. These nanoparticles are effective
hydroxychloroquine and also inhibited the proliferation of preclinically in carrying antigens such as HBsAg, malaria
rat lung fibroblasts, thereby, reducing pulmonary fibrosis. antigens tetanus toxoid, Listeria monocytogenes antigens,
This strategy can be adopted to have dual benefits in SAR- and Bacillus anthracis spores, generating prolonged
COV-2 patients, which show viral load and pulmonary cellular and humoral immune response. 9
fibrosis.
The mRNA-based COVID-19 vaccine is already under
Nanomedicine for Combination Drug Therapeutics clinical trial employing LNPs as a carrier. Naked mRNAs are
sensitive to the degradation by extracellular RNases, thus
Combination drug therapy is another possibility for
formulating its delivery vehicle is essential. LNPs are virus-
treatment of COVID-19, offering several advantages such
sized (80–200 nm) particles synthesized by the self-
as lower dosages of the individual drugs causing fewer side
assembly of an ionizable cationic lipid. They possess the
effects, achieving multiple and complimenting therapeutic
ability to deliver mRNA efficiently into the cytoplasm. An
targets, and reducing the likelihood of resistance
ongoing clinical trial (NCT04336410) is using a DNA plasmid
development. 9
encoding SARS-CoV-2 S-protein as a vaccine candidate for
Multidrug-loaded (anti-retroviral, latency reactivating intradermally administration using an electroporation
agents, and drug abuse antagonist) PEGylated-magneto- device (CELLECTRA 2000). 9
liposomal nano formulations have shown in vitro and in
Vaccine Adjuvant Nanoparticles
vivo BBB transmigration with significant anti-HIV activity in
primary CNS cells. This multifunctional nano-therapeutic Vaccine adjuvants nanoparticles (VANs) are considered to
strategy can be applied to target SARS-COV-2 that has improve the overall efficacy and safety of the generated
migrated to the CNS. 19,29 immune response. Vaccine adjuvants are critical to
reducing the required antigen dose (dose-sparing),
Plan to design nonvaccine for COVID-19
permitting the production of more units and making it
One of the bigger challenges in the COVID-19 vaccine available to the larger population. Informing specific
research is to identify approaches that stimulate both the immune cells to mount a protective immune response
T cell and B cell immunity against this virus. Another against a specific antigen is the basic mechanism of VANs
challenge is the necessity of accelerating the development designed to improve efficacy (by serving as immunity
of precise “next-generation” vaccine strategies that may promoting cues, also called as “danger signals”). In the case
also address specific population subgroups or individuals of a virus, these danger signals are characterized as PAMPs
with compromised immunity. 13 and damage-associated molecular patterns (DAMPs)
derived from the same virus. PAMPs and DAMPs are
The nano vaccine strategy also requires a strong focus on
recognized by specific receptors called pattern recognition
the cellular presentation of the selected antigen, along
receptors (PRRs). An example of such receptors is Toll-like
with the selection of appropriate nanocarrier/
receptors which are expressed by immune cells to
upregulate robust T and B cell priming by releasing Protein sub-unit vaccine

inflammatory cytokines. VANs can either act as a
Based on the synthetic peptides or recombinant antigenic
nanocarrier for molecular adjuvants or have an inherent
proteins, which are necessary for invigorating long-lasting
physicochemical property to stimulate pro- or anti-
protective and/or therapeutic immune response. [25]
immunity pathways. VANs are designed to tackle the
limitations related to the conventional delivery of Subunit vaccines are composed of purified antigens
molecular vaccine adjuvants such as rapid bloodstream instead of whole microorganisms, and different carriers
clearance, systemic distribution, and lack of immune cell serve as transporter for those antigens. In the anti-SARS-
targeting as well as lack of antigen-adjuvant co- CoV-2 subunit vaccines, the antigens are represented by
localization. VANs are an established strategy to achieve a viral proteins, peptides, or nanoparticles. Because of the
significantly high-dose-sparing effect, whereas DCs relatively low immunogenicity of the subunit vaccines,
targeting VANs may enhance its adjuvanticity. VANs adjuvants are required to create a stronger immune
(including PLGA, AuNPs) are also employed to co-deliver response. Subunit vaccines provide a high level of safety.41
self-antigens or immunoregulatory drugs as adjuvants to
Advax-SM (clinical trial #NCT04453852) is an adjuvant
induce antigen-specific peripheral tolerance of auto-
composed of polysaccharide delta-inulin and CpG
reactive T cells and block any serious autoimmune
oligodeoxynucleotide (CpG ODN). CpG ODN is a TLR 9
response. Nanoparticles because of their intrinsic
agonist with T-helper 1 skewing properties. The
adjuvanticity (by activating complement system, inducing
granulocyte-macrophage colony-stimulating factor is a
autophagy and activation of inflammasome) are also
pro-inflammatory cytokine that may also serve as an
considered as VANs. 9
adjuvant (#NCT03305341 and #NCT04386252). 31
Scope of miscellaneous nanotechnology approaches
The University of Queensland in collaboration
Advanced nanomaterial and biomimetic approaches with GSK and Dynavax is developing stabilized pre-fusion
represent good potential usage in a COVID-19-like recombinant protein subunit vaccine against SARS-CoV-2
outbreak. Functionalized carbon quantum dots (CQDs) to using its Molecular Clamp technology that locks the SARS-
inhibit the human coronavirus (HCoV-229E) infection. CoV-2 specific protein in the three-dimensional shape with
CQDs of different sizes (<10 nm), surface potential (−7.9 to the ability to develop a humoral immune response against
−39.2 mV), and functionalities were explored as inhibitors appropriate viral epitopes. Novavax has developed a
of Huh-7 cells (host cell) infection by HCoV-229E, and they protein subunit vaccine, NVX-CoV2373 by combining
showed a concentration-dependent virus inactivation. its nanoparticle technology. 30
Boronic acid-modified CQDs showed the maximum efficacy
The S protein of the SARS-CoV-2 is the most suitable
with an EC50 value of 5.2 ± 0.7 μg/mL, illustrating the
antigen to induce the neutralizing antibodies against the
significance of boronic acid functionality to inhibit the early
pathogen. The S Protein consists of two subunits. The S1
stage interaction of viral S-protein receptor with the host
subunit has the NTD, RBD, and RBM domains while the S2
cell membrane. 19
subunit comprises FP, HR 1, &2. The virus enters into the
Where are we at nano vaccines? cell via endocytosis by utilizing the S-Protein mediated
binding to the hACE2 receptor. Therefore, the S-Protein
The use of nanoparticles in vaccine formulations could
and its antigenic fragments are the prime targets for the
fulfill three different purposes: 21
institution of the subunit vaccine. 25
▪ Enhanced antigen stability by protecting them from
The S glycoprotein is a dynamic protein, possessing two
premature degradation by proteolytic enzymes
conformational states i.e. pre-fusion and post-fusion state.
▪ Enhanced immunogenicity as an immuno-stimulant Therefore, the antigen must maintain its surface chemistry
adjuvant to provoke an immune response and profile of the original pre-fusion spike protein to
preserve the epitopes for igniting good quality antibody
▪ Targeted delivery where nanoparticles are used as
responses. Moreover, the means to target the masked
delivery systems to facilitate antigen uptake and
RBM as an antigen will enhance the neutralizing antibody
processing by antigen-presenting cells.
response and improve the overall efficacy of the vaccine.25
Types of Nano Vaccines
NVX-CoV2373 (Novavax, Inc. Emergent BioSolutions)
Biomimetic nano vaccines
NVX-CoV2373 is a nano-particle-based immunogenic
Biomimetic vaccines contain biomimetic vehicles that are vaccine that is based upon the recombinant expression of
loaded with target antigens. Various types of biomimetic the stable pre-fusion, coronavirus S-Protein. The
nano vaccines such as lipid nanoparticles, protein University of Queensland in collaboration with GSK and
nanoparticles, and virus-like particles can be produced Dynavax is developing stabilized pre-fusion recombinant
with the aid of biotechnology, nanotechnology, or both. 36 protein subunit vaccine against SARS-CoV-2 using its
Molecular Clamp technology that locks the SARS-CoV-2
specific protein in the three-dimensional shape with the
ability to develop a humoral immune response against
appropriate viral epitopes. The company plans to use the and non-pathogenic viral capsid protein-based vaccines.
Matrix-M adjuvant to enhance the immune response VLPs can be either enveloped or non-enveloped.
against SARS-CoV-2 spike protein by the induction of high Enveloped VLPs contain viral proteins on their outer lipid
levels of neutralizing antibodies. membrane formed through budding from respective host
cells, whereas non-enveloped VLPs lack lipid layers and are
Molecular Clamp Stabilized spike protein vaccine
composed of one or more viral structural proteins. VLPs
candidate
can be decorated on their surface to display target antigen
It is being developed by the University of Queensland in using recombinant fusion protein expression or chemical
collaboration with GSK and Dynavax. The University will cross-linking with bi-functional linkers. VLPs also
have access to vaccine adjuvant platform technology (AS03 allow encapsulation of target antigenic gene or peptide
Adjuvant system), which is believed to strengthen the fragment for the immune cell presentation and activation.
vaccine response and minimize the amount of vaccine VLPs can be loaded with single or multiple capsid proteins
required per dose. The University is developing a stabilized and can be formulated in different diameters ranging from
pre-fusion, recombinant viral protein sub-unit vaccine 20 to 200 nm. VLPs hold all the conformational epitopes to
which is based upon the Molecular Clamp technology. This the native virus to allow repetitive antigen presentation.
technology has been proved to induce the production of
Several VLP nano vaccines have been tested preclinically
neutralizing antibodies. 25
against β-coronaviruses.
Triple Antigen Vaccine (Premas Biotech, India)
MERS-CoV VLP vaccine was prepared by assembling viral S
It is a multi-antigenic VLP vaccine prototype wherein the protein on the surface of nanoparticles (100-200 nm)
recombinant spike, membrane, and envelope protein of secreted from the BM5 insect cells that co-express viral E
SARS-CoV-2 have been co-expressed in an and N proteins using mechanical extrusion. The resulting
engineered Saccharomyces cerevisiae expression platform VLPs express all the viral components, S, E, and N proteins,
(D-Crypt™). The proteins then undergo self-assembly as and can bind human dipeptidyl peptidase 4 (DPP4) which
the VLP. The TEM and allied analytical data simultaneously is the target receptor for the MERS-CoV host entry.
furnished the biophysical characterization of the VLP. This
A recombinant SARS-CoV VLP nano vaccine containing
prototype has the potential to enter the pre-clinical trials
both the SARS-CoV S and influenza M1 proteins produced
as a vaccine candidate after further research and
using the baculovirus Sf6 insect cell expression system was
development.
shown to elicit an immune response in mice with a
PittCoVacc (University of Pittsburgh) reduction in lung virus titers to below detectable levels
when administered intramuscularly or intranasally.
It is a Micro-Needle Array (MNA) based recombinant SARS-
CoV-2 vaccine that involves the administration of rSARS- Virus mimicking particles have garnered great attention for
CoV-2 S1 and rSARS-CoV-2-S1fRS09 (recombinant vaccine development because they can trigger a strong
immunogens). The immunogenicity of the vaccine was immune response. Because the particles resemble the size,
maintained even after the sterilization using gamma form, and structure of viruses’ shells, they mimic the
radiation. The statistically significant titers of antibodies at essential viral features suitable for vaccination. Another
the early stages and also before boosting, support the advantage of these viral particles is that they are non-
feasibility of the MNA-SARS-CoV-2 vaccine. 25 infectious as they lack nucleic acids. But the eminent
disadvantage of this technology is associated with the
NP-Based Vaccines - Virus-like particles (VLPs)
manufacturing challenges of vaccines as the virus-like
Nano-sized VLPs, which have the characteristic function of particles are produced in heterologous host systems.33
the virus, have the advantage of being better delivered
Although many virus-like particles-based vaccines against
through the lymph and capillaries than other small
viral infections have been undergoing clinical trials, only a
vaccines. It has the effect of reducing the systemic
few of them have been licensed and commercialized. 46
inflammatory response, and similar to viruses, has the
advantage of being able to very easily enter cells. Engerix-B (GlaxoSmithKline) was the first virus-like
Therefore, the synthesized complex recognized by the T particles vaccine developed for hepatitis B virus (HBV)
cell receptor increases the vaccine’s immunogenicity and which was licensed in 1986. Similarly, Cervarix
efficacy, thereby ensuring patient safety. 293 Nano-sized (GlaxoSmithKline) was licensed in 2009 for the prevention
VLPs entering the host cell are directly involved in B cell of human papillomavirus (HPV), and Hecolin (Xiamen
activation and boosting the immune system.292,295 Innovax) to protect from hepatitis E virus was licensed in
Indeed, the characteristics of these synthetic nano-sized 2012. No doubt, coronavirus-like particles with targeted
VLPs are the principle of developing vaccine structural proteins could be a potential vaccine candidate
platforms.296–298 Nano-sized VLPs have also been for COVID-19 control. The assembly of viral membrane
reported to overcome viruses by increasing the immune proteins into particles has been well studied.
response effectively in animal experiments. VLPs are
In a study, a recombinant host cell was made to express
structurally identical to the virus particles but lack a viral
coronavirus membrane proteins which assembled into
genome. Therefore, VLPs are termed as non-replicating
particles and released from the cell. The released particles polymers and different forms of nuclei acids. The
were spherical and identical to corona virions in size (100 polyplexes form nanoparticles of various sizes and shapes
nm) and shape. The study also revealed that the small with possible surface modifications. Therefore, the
envelope protein (E) and the membrane glycoprotein (M) polyplexes have diverse applications in drug, gene, and
were required for particle formation while the spike vaccine delivery. 46
protein (S) and the nucleocapsid protein (N) were
Often, nucleic acid-based vaccines use LNPs to avoid the
dispensable. The results were consistent with another
degradation of nucleic acids when administered in the
study which demonstrated that the viral membrane
body.
proteins E and M when expressed together in eukaryotic
cells, assembled into coronavirus-like particles. mRNA Vaccine
Similarly, coronavirus-like particles that express one or mRNA is an emerging, non-infectious, and non-integrating
more structural proteins of SARS CoV were produced using platform with almost no potential risk of insertional
a heterologous expression system. In this study, a mutagenesis. Currently, the non-replicating RNA and the
recombinant virus was used to express a high level of S, E, virus-derived self-replicating RNAs are being studied. The
and M proteins simultaneously which self-assemble to immunogenicity of the mRNA can be minimized, and
produce and release the coronavirus-like particles. 6 alterations can be made to increase the stability of these
vaccines. The stabilization is further achieved by various
Nucleic acids vaccines
transport systems (such as lipid nanoparticles, nano-
Currently, vaccines using nucleic acids (DNA or RNA), based emulsions, and cationic peptides) or methods enabling
on the nanotechnology approach, are aiming to help fight facilitated transfection (gene gun and electroporation).9
against coronavirus. The nucleic acids are often
The mRNA-based nano vaccines have benefits over other
encapsulated in a lipid coat to insert into human cells.
technologies which include short development time,
Following the internalization in the cells, the nucleic acids
simple manufacturing and purification processes
are converted into the targeted virus proteins, mostly
regardless of the antigen, and most importantly, mimic
spike proteins. These foreign proteins induce danger
natural infection to promote potent cellular and humoral
signals to the immune system and trigger antigen-
immunity by eliciting CD4 and CD8 T cell responses.
presenting cells to engulf them. Then these engulfing cells
Multiple mRNAs can be combined into a single vaccine to
display the foreign proteins to T cells and B cells to activate
deliver mRNA transcripts of interest into the host cell
the short and long-term immunity. Nucleic acids vaccines
cytosol, which allows the encoding of one or more
are safe and less reactogenic. Due to the advancement of
antigen(s). 30
nanotechnology, these vaccines are easy to develop and
free from complicated processes of manufacturing. Many Mainly two types of mRNA constructs have been
biotech companies are well known for their expertise in evaluated: self-amplifying mRNA and non-replicating
the targeted delivery of mRNA therapeutics using multiple mRNA.
mRNA delivery formulations. Depending upon the
mRNA-1273 (Moderna TX, Inc)
therapeutic application and route of delivery, various
formulations can be designed as follows: It is a vaccine composed of synthetic mRNA encapsulated
in Lipid nanoparticle (LNP) which codes for the full-length,
Lipid Nanoparticles (LNPs)
pre-fusion stabilized spike protein (S) of SARS-CoV-2. It has
The formulation is made by encapsulating mRNAs in LNPs. the potential to elicit a highly S-protein-specific antiviral
LNPs can be modified externally with various proteins or response. 25
chemicals for targeted delivery. LNPs can transfer the
BNT162b1 (BioNTech| FosunPharma| Pfizer)
encapsulated mRNAs inside the human cells to express the
target antigens. 26 BNT162b1 is a codon-optimized mRNA vaccine that
encodes for the trimerized SARS-CoV-2 RBD, a critical
target of the virus nAb. The vaccine portrays increased
Lipoplexes immunogenicity due to the addition of the T4 fibrin-
derived fold on the trimerization domain to the RBD
The formulation is a complex of embedded mRNA in a lipid
antigen. The mRNA is encapsulated in 80 nm ionizable
bilayer. The size and charge of the lipoplexes can be
cationic lipid nanoparticles, which ensures its efficient
modified by changing the ratio of negatively charged
delivery. 25
mRNA and cationic lipids. The lipoplexes are served to
deliver mRNA to target cells such as dendritic cells in DNA Vaccines
immune compartments for antigen presentation to
The most revolutionary approach to vaccination is the
activate the immune system.
introduction of the DNA vaccine which encodes for the
Polyplexes antigen and an adjuvant that induces the adaptive immune
response.
The formulation is a polymer complex of nuclei acids. The
polyplexes can be formed from a wide variety of cationic
The transfected cells express the transgene which provides Existing viral vectors can be divided into two categories:
a steady supply of the transgene-specific proteins which is replicating (replication-competent) and non-replicating
quite similar to the live virus. Furthermore, the antigenic (replication-deficient).[25] The replicating viral vector
material is endocytosed by the immature Dendritic Cells produces infectious viruses capable of infecting target
which ultimately present the antigen to the CD4+ and cells to produce viral antigens. AD26 associated vaccine
CD8+ T cells in association with MHC 2 and MHC 1 antigens against SARS-CoV-2 showed complete protection in rhesus
on the cell surface hence stimulating effective humoral as macaques after infection. Thereafter, a series of AD26
well as cell-mediated immune responses. 25 vectors encoding different SARS-CoV-2 spike protein
epitopes were developed with encouraging outcomes.
DNA vaccines deliver coronavirus genes to the human
Recently, Russia approved a COVID-19 vaccine Sputnik V
cells. The vaccination principle depends on the DNA
exhibiting two different adenovirus vectors (rAd26 and
translocation into the cell nucleus where the transcription
rAd5), both carrying the gene for SARS-CoV-2 S
of the antigen is initiated and followed by a translation.
glycoprotein (rAd26-S and rAd5-S). 25
DNA vaccines frequently use plasmids as vectors.
Depending on the route of vaccine administration Developed by Gamaleya Center in Russia, the two-vector
(intramuscular, intradermal, and subcutaneous), either vaccine, as the name suggests, uses two different vectors
myocytes or keratinocytes are addressed. 42 (Ad5 and Ad26). Vector development involves the use of S-
protein mRNA to generate the complementary DNA,
DNA vaccines are a harmless complement to conventional
followed by insertion of this S-protein encoding DNA
live- and inactivated-virus vaccines. DNA vaccines are
into adenoviral vectors, Ad26 and Ad5. Ad26 vector
generally safe and stable compared to conventional
encoding S-protein was administered as the first
vaccines because the vectors used are non-replicating and
vaccination followed by a booster dose of Ad5 vector
express only the antigen of interest. Therefore, unlike viral
encoding the same S-protein 21 days later. Inside the
vector vaccines, they are not able to revert to the disease-
recipient, these vectors generate the S-proteins, which
causing form. DNA vaccines also lack vector-induced
upon entering the circulation induce protective immunity.
immunity which allows their use with other vaccines in the
The illustration is prepared in-house and schematic ideas
same individual. In short time intervals, DNA vaccines are
and technical details were followed as presented in the
produced in bulk quantities. 25
previously published report. 25
INO-4800 (Inovio Pharmaceuticals)
Ad5-nCoV (CanSino Biologics Inc | Beijing Institute of
It is a prophylactic DNA vaccine against SARS-CoV-2. It uses Biotechnology)
a codon-optimized S protein sequence of SARS-CoV-2 to
It is a recombinant, replication-defective adenovirus type-
which an IgE leader sequence is affixed.
5 vector (Ad5) expressing the recombinant spike protein of
5.4 Viral Vectored vaccines SARS-CoV-2. It was prepared by cloning an optimized full-
length gene of the S Protein along with the plasminogen
A vaccine based on viral vectors is a promising prophylactic
activator signal peptide gene in the Ad5 vector devoid of
solution against a pathogen. These vaccines are highly
E1 and E3 genes. The vaccine was constructed using the
specific in delivering the genes to the target cells, highly
Admax system from the Microbix Biosystem.
efficient in gene transduction, and efficiently induce the
immune response. They offer a long term and high level of Coroflu (University of Wisconsin-Madison | FluGen |
antigenic protein expression and therefore, have a great Bharat Biotech)
potential for prophylactic use as these vaccines trigger and
M2SR, a self-limiting version of the influenza virus, is
prime the cytotoxic T cells (CTL) which ultimately leads to
modified by the insertion of the SARS-CoV-2 gene
the elimination of the virus-infected cellsViral vector-
sequence of the spike protein. Furthermore, the vaccine
based vaccines (VBVs) are constructed by engineering a
expresses the hemagglutinin protein of the influenza virus,
viral vector to carry coronavirus genes and slowly replicate
thereby inducing an immune response against both
in the host cells. The replication leads to the production of
viruses. The M2SR is self-limiting and does not undergo
coronavirus proteins and subsequent immune system
replication as it lacks the M2 gene. It can enter into the cell,
activation. Potential viral vectors include a broad spectrum
thereby inducing immunity against the virus. It shall be
of both DNA and RNA viruses. 22
administered intra-nasally, mimicking the natural route of
These viral vectors can be constructed as replicating or viral infection. This route activates several modes of the
non-replicating vectors In SARS-CoV-2 vaccine immune system and has higher immunogenicity as
development, the most commonly used vectors are the compared to intramuscular injections. 25
adenoviral vectors, such as ChAdOx (#NCT04536051 and
LV-SMENP-DC (Shenzhen Geno-Immune Medical
#NCT04516746), adenovirus type 5 (#NCT04564716,
Institute)
#NCT04540419, and #NCT04526990), and adenovirus type
26 (#NCT04564716 and #NCT04505722). All these vaccines The LV-SMENP-DC vaccine is prepared by engineering the
are currently being evaluated in phase III clinical trials. dendritic cells (DC) with the lentiviral vector expressing the
conserved domains of the SARS-CoV-2 structural proteins

and the protease using the SMENP minigenes. The Virus multiplication is often followed by purification and
subcutaneous inoculation of the vaccine presents the concentration before the vaccine inactivation.
antigens on antigen-presenting cells (APCs) that ultimately Formaldehyde and beta-propiolactone are used in the
activate the Cytotoxic T cells and generate the immune majority of licensed human antiviral vaccines to inactivate
response. 25 the virus. Multiple doses or adjuvants are required to
achieve sufficient efficacy of inactivated vaccines. To date,
ChAdOx1 (University of Oxford)
4 inactivated vaccines have reached the phase III clinical
ChAdOx1 recombinant adenovirus vaccine was developed trials and are currently under evaluation (#NCT04510207,
using codon-optimized S glycoprotein and synthesized #NCT04508075, and #NCT04456595). 22,23
with the tissue plasminogen activator (tPA) leader
Whole inactivated vaccine
sequence at 5’ end. The sequence of SARS-CoV-2 coding
for amino acids (2 to 1273) and the tPA leader and was Whole inactivated vaccines are composed of chemically or
propagated in the shuttle plasmid. radiationally inactivated virions. They contain a full
repertoire of immunogenic components of the original
The Adenovirus vector genome is constructed in the
virus, and compared with attenuated viruses, they carry no
Bacterial Artificial Chromosome by inserting the SARS-CoV-
risk of viral reactivation if properly inactivated. Although
2 S gene into the E1 locus of ChAdOx1 adenovirus
safer than live attenuated vaccines, the immunogenic
genome.15
epitopes of inactivated viruses may be structurally
Live Attenuated Vaccines deformed during the inactivation process, which can
undermine the protection they may provide. Moreover,
These use live viruses to elicit protective immune
both SARS-CoV and MERS-CoV whole inactivated vaccines
responses. Live vaccine raises the possibility of viral
have been reported to induce eosinophil-related lung
virulence reversal. Therefore, live virus vaccines need to be
pathology. These disadvantages make whole-inactivated
developed by altering the viral genome and selecting non-
vaccines a less attractive strategy for coronavirus vaccine
pathogenic mutant strains incapable of causing disease.
development. Currently, there are 7 whole inactivated
Live virus vaccines can also be produced by viral
COVID-19 vaccines in clinical trials. 26
attenuation. These are viruses weakened in
their pathogenicity but can elicit antiviral immune Whole Inactivated Virus Vaccine of SARS-CoV induces
responses without causing disease. eosinophilic pro-inflammatory pulmonary response.
Immunization with SARS-CoV virus-like particle (VLP)
DelNS1-SARS-CoV2-RBD (University of Hong Kong)
vaccine leads to eosinophilic immunopathology in the lung
This LAV is an influenza-based vaccine strain with a after viral challenge. They found that appropriate
deletion in the NS1 gene. It is re-organized to express the adjuvants, such as Toll-like receptor agonist and delta-
RBD domain of SARS-CoV-2 spike protein on its surface inulin polysaccharide, can increase serum neutralizing
and, is cultivated in the chick embryo and/or Madin Darby antibody titers and reduce lung eosinophilic
Canine Kidney Cells (MDCK) cells. It is potentially more immunopathology. Their results provide a promising
immunogenic than the wild type influenza virus and can be strategy to deal with the T2-skewed immune response
administered as a nasal spray induced by some CoV vaccines. 26
Inactivated vaccines Others
These viruses are inactivated by radiation, heat, and The revelation of the structure and genome of the SARS-
chemicals such as binary ethyleneimine and formalin. This CoV-2 has led to the rapid development of various vaccine
leads to an inability to cause illness. However, inactivated candidates with potential immunogenicity but also
viruses maintain the ability to induce host immunity that adverse reactogenicities. The task of vaccine development
recognizes and destroys pathogens. This vaccine type is long and cumbersome which requires evaluation in some
contains viral particles from inactivated virus and hence do long-lasting clinical trials.
not develop pathogenicity. The inactivated
Various Biotech ventures are using different technologies
vaccine developed against poliovirus is an example, where
for the development of their vaccine candidates; British
the virus is inactivated by formaldehyde treatment. Nine
and American Tobacco Company (BAT) recently unfolded
SARS-CoV-2 vaccines are being developed using this
the COVID-19 vaccine using their new, and fast-growing
technology. Sinovac Biotech is developing inactivated
tobacco plant technology, while Tianjin University has
vaccine PiCoVacc which is now known as CoronaVac
developed an oral vaccine that has successfully
against SARS-CoV-2 and this candidate induces broadly
employed Saccharomyces cerevisiae to carry the S protein.
neutralizing antibodies against ten different viral strains in
The GRAS (Generally Regarded as Safe) status of the yeast
multiple species that include primates. 35
provides high scalability, robustness, and cost-effective
Inactivated vaccines are based on presenting the form of production of cosmic dosages required to fight off this
the pathogen with a loss of disease-producing capacity. pandemic. Furthermore, in silico studies, using various
The virus cultivation occurs in cell lines that represent a databases like VaxiJen, have revealed that the epitope
substrate for the production of large quantities of antigen.
sequences WTAGAAAYY and YDPLQPEL can be employed eradicate the reactive moieties. Sometimes, it could be
for the formulation of epitope-based peptide vaccines. caused directly due to the generation of ROS within the cell
or indirectly disturbing the mitochondria respiration, or
Self-Assembling Vaccine (HaloVax)
reduce the antioxidant moieties inside the cell
The vaccine uses a heat shock protein (hsp) to activate the environment. The hindrance of oxidative stress might act
immune system. It is composed of a fusion protein as a significant phase in initiating few harmful
sandwiched between an hsp and Avidin. Biotinylated pathobiological activities within the cellular micro-
immunogenic peptides are also incorporated to customize environment. Moreover, the effect of NPS over the
the vaccine. 25 oxidative stress conditions in the animal models or at the
cellular level is usually considered as a common endpoint
Safety and Hazards of Nano Vaccine
study to detect the toxicity profile of NPs. Both in vivo and
The accumulation of therapeutics at nontargeted or in vitro studies play a crucial role in understanding the
undesired locations is one of the most difficult problems in mechanisms of NPs causing oxidative stress. For example,
the treatment of COVID-19. By using active targeting of studies have shown significant accumulation of titanium
nano-vehicles to guide therapeutics to the targeted site of dioxide NPs (TiO2-NPs) in the lungs of mice after a 90-day
action, this may be greatly reduced. It is also feasible to successive intra-tracheal administration of TiO2 NPs. The
target intracellular and cellular sites, as well as specific TiO2-NPs expressively enhanced the accumulation of ROS
organs, such as cathepsin binding sites, ACE2 expressing level, inflammation, lipid peroxidation level, and also
cells, and viral S protein domains, all of which are involved reduced the antioxidants competency in the lungs. The
in SARS-CoV-2 pathogenesis. The controlled and sustained NPS could produce ROS followed by oxidation of
release of drugs from nano vehicles can improve patient antioxidant moieties, and thus could influence the
compliance, reduce adverse effects, reduce dose quantity respiratory system and associated pathobiological
and frequency, and lower the danger of viral rebound activities including pulmonary inflammation and
during viral infection therapies. 42 genotoxicity. 38
What are the risks associated with nanotechnology? In some cases, it has been observed that the NPs,
administered through the nasal route, caused chronic or
Nanotechnology is potentially hazardous for three
acute inflammation-mediated processes such as the
reasons: 5,7,16
inclusion of inflammatory cells and proclamation of
1. Nanoparticles (NPs) may cause lung damage: ultra- cytokines. In one of the studies, it was noticed that the
fine particles. direct administration of graphene oxide (GO) solution into
the lungs of C57BL/6 mice caused extreme pulmonary
2. Carbon nanotubes inhaled can suppress the immune
inflammation with alveolar exudate. The NPs are involved
system by altering the activity of T- cells, a kind of
in triggering few pro-inflammatory pathways, including
immune cell that helps the body fight infections.
mitogen-activated protein (MAP) kinases. The NPs-treated
3. Brain damage - Discrete nanometer-sized particles cells have shown an increased level of AP-1 (activator
were deposited in the nasal cavity (in this case in rats), protein-1) transcription factors and NF-κB (nuclear factor
completely bypassing the blood-brain barrier and kappa enhancer of triggered B cells), thus affecting the
traveling up the olfactory nerves straight into the DNA transcription, production of cytokines, and survival of
brain. cells. 38
Overall, the importance of nanotechnology and Genotoxicity, either primary or secondary, is a major
nanoscience cannot be overstated, yet these promising concern when using NPs to deliver drugs. The genotoxic
materials have the potential to create serious problems in moieties or NPs influence directly by attaching to DNA
the lungs and respiratory systems. structures or constituents of cellular division such as the
microtubule spindle or centromere. Carbon nanotubes
Cell toxicity, fibrosis, inflammation, oxidative stress,
(CNTs) have made direct contact with DNA assemblies. This
genotoxicity, and immunotoxicity are the six primary
indicated that CNTs might be genotoxic in vivo (in animal
pathobiological factors that must be considered when
models) or at the cellular level. According to studies,
employing nanoparticles or related methods to treat
inhaling multi-walled CNTs induced genotoxicity by
present and future coronavirus infections.
generating chronic inflammation, which resulted in
Despite extensive research on nanotechnology-based persistent oxidative stress. 38
methods (polymeric, inorganic self-assembling materials,
Fibrosis is an indication of an accumulation of inhaled NPs
PBNPs, and nano vaccine) to combat COVID-19, there have
in the lungs, and it can lead to unusual forms of pulmonary
been significant disadvantages, including cost, time, and
inflammation including eosinophilia. In one study, single-
possible cell toxicity of these nanoparticles. 42
walled CNTs inhaled into the lungs of C57BL/6 male mice
The oxidative stress typically arises due to disparity produced multifocal granulomatous pneumonia and
amongst the reactive oxygen species (ROS) production and fibrosis.
the capability of a biological system to voluntarily

There are immuno-pathological problems linked with the ✓ Nano-vehicles are being used in combination
SARS-CoV vaccines that need to be addressed and therapeutics.
improved. 26
✓ Decorating specific (nano) targeting moieties on the
➢ The production of antibody-dependent enhancement surface of nanomaterials allows for active targeting.
(ADE) effect, which is generally produced by vaccine-
✓ Rapid detection with nano-biosensors.
induced inadequate antibodies that aid viral entrance
into the host cell, is one of the side effects. Design ✓ Surface coatings having antiviral properties created
vaccines that only include significant neutralizing by incorporating nanoparticles into the polymer
epitopes, such as the S1 subunit or the RBD domain of matrix.
the S protein, to address the ADE issue. This approach
✓ Nanomaterials' capacity to act as disinfectants.
can decrease the ADE impact by reducing the induction
of non-neutralizing antibodies by CoV vaccines. ✓ Developing vaccines with nanomaterials and
chemically altering/reengineering medicines. 42
➢ Vaccine-induced eosinophilic immunopathology, which
is an undesirable T2-skewed immunological response Nano vaccine’s Drawbacks
generated by vaccination, is another potential adverse
1. Due to the restrictions of nanoparticles in vaccine
effect. 26
manufacture, the toxicity, and difficulty in presenting
These particles are toxic at the molecular, cellular, and naive antigens are often mentioned 28. The
tissue levels. 43 manufacturing of nanoparticles is hard to process 35.
✓ At the tissue level: inflammation - damage may One of the harder processes is scaling up nano
occur. polymers 18. However, with the introduction of the
latest techniques like scaled-up methodology for spray
✓ At the cellular level: reactive oxygen species -
drying, certain scale-up difficulties are overcome, yet
disruption of compartments.
during a one amongst one in every of one among the
✓ At the molecular level: conformational change, loos foremost significant issues facing nano vaccines are
of function, and aggregation. scaling up in a sterile environment 39.
Nanomedicine toxicity has been examined numerous 2. Nanoparticles' small size allows them quick access to
times. Carbon-based nanoparticles, for example, have numerous biological tissues and organs, which could be
been shown to have a variety of laboratory and clinical a double-edged sword 36. Intradermal injections of the
toxicities, and carbon nanotubes have been shown to nano vaccine can cause dermatological problems; oral
cause mesothelioma. Surprisingly, the toxicity was administration can cause gastrointestinal problems,
ascribed to its form rather than the elements themselves.43 and nasal delivery might cause respiratory difficulties
44
The biocompatibility of drugs is also determined by the size . Cardiovascular problems also can be caused by the
of nanoparticles. Au nanoparticles, for example, were toxic parenteral method 37. Furthermore, if these
at 1.4 nm but not at 15 nm. Ag nanoparticles have also nanomaterials are ready to transit the barrier, they'll
been proven to have toxic effects. Because iron can induce brain injury 27. The aggregation of nanoparticles
accumulate in the immune system, the majority of the could trigger vascular thrombosis, consistent with a rat
toxins identified in NMPs were related to iron nanoparticle study 41.
toxicity. 11 3. On the opposite side, the utilization of nanoparticles in
This toxicity has been reported to be reduced in a variety vaccines might cause nanoparticle accumulation within
of ways. The addition of hydroxyl groups to gadolinium the cell, which may cause problems, particularly in
fullerene particles, for example, can prevent the long-term exposures 18. Quantum dots, for instance,
production of reactive oxygen species (ROS). Iron oxide are shown to remain within the body for up to 2 years
nanoparticles with polymer coatings can also improve cell during a rat research 40.
viability significantly. Selective targeting and preservation 4. Despite the very fact that ISCOMS are utilized during a
of healthy organs are the most important steps in reducing sort of vaccination, the utilization of saponin-based
their side effects. Surface modification is another option
[51] adjuvants in humans has been restricted thanks to their
.
toxicity 20. The usage of nanoparticles in humans
Nanotechnology-based ideas to combat COVID-19 in the remains a source of worry 22.
future: 5. Nano vaccines may create additional toxicity and other
✓ The potential of nanoparticles to circumvent the risks of their own, which might need to be addressed
traditional restrictions associated with antiviral drugs concurrently with nano vaccine development,
is used in the design and development of successful influencing their design and testing 29.
COVID-19 treatment. 6. Biopersistance is often a double-edged sword because
a vaccine must work for an extended time before

booster injections are required, but persistent adverse 17. Researchers are performing on developing greater
effects are unacceptable [23]. throughput assays for chemical fingerprints that
7. Nanoparticle adjuvants for vaccines must be created to would indicate long-term issues with nano vaccines 44.
reinforce vaccine absorption and immunogenicity, but 18. However, obtaining accurate chemical markers is
they need to also biodegrade as quickly as feasible, difficult, and our knowledge of the long-term effects
whereas conventional vaccines don't require of nanoparticle exposure is comparatively limited 29.
biodegradation 28. 19. Research into their function and therefore the
8. Because the system operates at the nanoscale, particular mechanisms of nano vaccine are limited 40.
therapeutic enhancement frequently veers perilously 20. Nanomedicine toxicity, scaling-up processes, and a
on the brink of unintended toxicity; many nanoparticles scarcity of regulatory requirements are all potential
are easily picked up by phagocytes, which can or might hindrances within the development of nano
not be what the designer intended, counting on the vaccines38.
condition being vaccinated against it 37. 21. Nanoscale size is often a double-edged sword since
9. An autoimmune response against the system is going preclinical and clinical studies on nano vaccines
to be triggered if nanoparticles are mistakenly revealed dose-dependent acute and chronic toxicities,
identified as foreign, leading to harmful effects and also as preferential bioaccumulation counting on the
even death 40. route of administration 36.
10. Nanoparticles also interact with other critical immune 22. Only a couple of sorts of nanoparticles, like inorganic
mechanisms, like the complement system, whose nanoparticles, have inherent toxicity after prolonged
activation by nanoparticles might be deleterious, like in exposure (e.g., metallic nanoparticles) 37.
tumor locations, where complement activation is 23. ISCOMS are employed during a sort of animal
understood to market tumors 29. vaccinations, but their use in humans was forbidden
11. Some challenges with risk management are unique to thanks to the toxicity of saponin-based adjuvants. As
developing countries: a result, there are still worries about the utilization of
a) Traditional markets are being displaced 28. nanoparticles in vaccines 31.
b) Foreign values are being imposed 28. 24. Scaling up is another key issue that has been
c) Concerns that technology advancements are going somewhat mitigated by technical developments, but
to be unrelated to development goals 28. scaling up during a sterile environment remains a
d) Inadequate resources for establishing, monitoring, considerable obstacle 18.
and enforcing safety rules 28. 25. a previous assessment of autoimmune adverse effects
12. If a household can afford the medications to caused by nano vaccine-induced immune activation is
successfully treat a disease after it strikes, seeking out required. Overactivation of antigen-presenting cells
vaccination against sickness might not be considered a by nano vaccine is often harmful because it can cause
priority 40. dendritic cell mortality 40.
13. Eliminating the disparity in nano vaccine can't be as 26. The increased complexity, manufacturing cost, and
simple as offering resources to everyone without also commercialization hurdles related to nano vaccine
considering how local people understand and use these treatment necessitate solutions to minimize these
services 39. restrictions 28.
14. Because certain possible hazards are yet unknown, the 27. Multiple loading of diverse components like antigens
subsequent are the first concerns of nano vaccine and adjuvants during a single nanoplatform is hard
technologies: and demanding 44.
a) Variations in toxicology/biocompatibility 25. 28. Thanks to their stability and cost-effective
b) Reproducibility of nano formulations on a broad manufacture in an efficient manner from batch to
scale 25. batch, scaling up nano vaccines is additionally an
c) Toxicological concerns, notably long-term organ enormous difficulty 27.
accumulation 15. 29. Because inhalation is that the commonest channel of
15. Nanoparticle toxicity is difficult to quantify, especially access for humans, the method of nanoparticle
when trying to quickly screen an outsized number of aggregation in inhaled air within the context of nano
nano formulations for vaccines or other medications vaccine is often detrimental 28.
38
. 30. When the dimensions of a chemical are reduced to the
16. Many of the negative impacts of nanoparticles on nanoscale level, the surface-to-volume ratio
humans are thought to be the consequence of long- skyrockets, leading to more molecules of the chemical
term, low-level exposure, which is difficult to quantify being present on the surface, increasing the intrinsic
and requires extensive testing 37. toxicity 37.

31. In comparison to barium sulfate when dosed at mass carefully adjusted, they will be harmful to human
burden in milligrams, titanium dioxide caused more health 44.
severe lung inflammation and particle lymph gland 38. The repetition of the assembly of water-soluble nano-
burden in trials of low toxicity particles 18. size formulations, also because of the combination
32. Lung irritation could also be a side effect of inhaled and discovery of immunological responses, issues
nanoparticles about nano vaccine 18 during this nanotechnology that require to be
33. Several hypotheses are offered to elucidate the addressed through follow-up clinical trials 26.
negative health impacts of nanoparticles, including: - 39. Nano vaccines may cause toxicity if they're not cleared
for an extended time 23.
Particle characteristics
40. Other big hindrances are unchanging production,
• the necessity of a broad area for interactions with transit, and storage 29.
cells and tissues 37. 41. Nanoparticles have the power to pass the barrier,
• The creation of complexes with biomolecules 40. which may be a significant disadvantage because
• In comparison to greater particles, a better level of nanoparticles employed to move medications might
radical species is formed 13. be hazardous to the brain 22.
• Increased oxidative stress induction 40. 42. For determining the interaction of hazardous effects
• Cellular DNA damage is induced 23. of nanoparticles with biological systems, doses are
• Lipid peroxidation induces oxidative stress 29. quantified in terms of the mass because the adverse
• Distribution: - effects of any substance are hooked into the mass of
• Size-dependent deposition properties 26. the substance 39.
• Uptake by respiratory epithelial cells 28. 43. A recent study revealed that carbon nanotubes have
• Increased interstitial space access 39. high toxicity, implying that they cause harm via a
• circulation access 44 unique mechanism, distinct from that of poisonous
• Organ system effects including effects on immune & dust 36.
inflammatory systems: - 44. Induction of oxidative stress in cells and organs is
• Reduced macrophage function, reduced particle assumed to be one mechanism of nanoparticle toxicity
38
phagocytosis, reduced macrophage mobility, and .
cytoskeletal dysfunction 10. 45. The toxicological study should include testing for
nanoparticle interactions with proteins and various
• Increased pro-inflammatory activity and production
cell types 37.
of cytokines and other mediators 45.
46. Reducing the dimensions to the nanoscale level leads
• Negative effects on cardiac functions and vascular
to a huge rise within the surface-to-volume ratio,
homeostasis 18.
which suggests that more chemical molecules are
34. Metals that are not particularly dangerous on their
present on the surface, increasing the intrinsic toxicity
own might be poisonous when breathed as
40. in comparison on a mass dosage basis, this might
nanoparticles 36.
be one among the explanations why nanoparticles are
35. The nerve olfactory is another possible pathway for
generally more harmful than bigger particles of an
inhaled nanoparticles to enter the body; nanoparticles
equivalent insoluble material 29.
may pass the mucosa inside the nose then attend the
47. Nanotubes are a specific sort of fiber with a diameter
brain via the olfactory nerve 27. within the case of
of a couple of nanometres but a length of several
poisonous nanoparticles in nano vaccine, this might be
micrometers. The carcinogenic effects of particular
damaging to the human body 37.
asbestos fibers should be considered while assessing
36. tract disorders and other contaminants can alter the
risks 45.
pulmonary inflammation and oxidative stress caused
48. Nanoparticles could also be ready to translocate from
by nanoparticles within the elderly 29.
the lungs into the bloodstream, exposing internal
37. Nanoparticle toxicity is decided by their chemical
organs to varying degrees of systemic exposure.
makeup, also because the chemical makeup of any
Inducing an inflammatory response might cause
substances adsorbed onto their surfaces 28. If the
neurological reactions that are damaging to the
chemical composition of nanoparticle surfaces isn't
human body 23.

Table 2: List of Nano vaccines under clinical trial

Name of vaccines Type of vaccines Phases Remarks
Phase I The first vaccine completes the preclinical trials and enters the human clinal
(LNP)-encapsulated trials. The vaccine is found to be safe and effective in volunteers aging
mRNA-1273 Phase II
modified mRNA between 18-55 years. After getting positive results from the phase I and II
trials now started dosing the vaccine for phase III trials. 10,35
Phase I was conducted in the US and Germany approved that the vaccine is
safe and has high immunogenic properties. Now BioNTech and Pfizer are
BNT162b2 3LNP-mRNAs Phase III
recruiting volunteers from the US, Brazil for the conduction of phase II/III
trials. 41
Phase I clinical trials was conducted in Australia. After the trials, the vaccine
Recombinant protein
NVX-CoV2373 Phase II is termed as safe and is capable of producing antibody responses against
nanoparticle vaccine
SARS-COV-2. Now the phase II clinical trials are conducting in South Africa. 38
In Phase 1 clinical trial is started with 40 healthy volunteers where 94% of
Phase I participants showed protective immunogenic responses six weeks after two
INO-4800 DNA plasmid vaccine /Phase II doses (1 and 2mg) of INO-4800. 32 After the early satisfactory results, Inovio
is now recruiting healthy participants for the conduction of the Phase 2/3
trial in South Korea and China. 11
Phase I In the pre-clinical studies, the vaccine shows all the potency requirements
Covigenix DNA vaccine /Phase II i.e. high immunogenic responses, safety, and efficacy. So, after completing
the preclinical trials now the vaccine is about to enter phase I/II trials. 13
Phase I Vaccine shows positive and protective immunogenic results in mice, rats,
ZyCov-D plasmid DNA vaccine /Phase II guinea pigs, and rabbits, now the company is enrolling healthy volunteers
for phase I/II trials. 62
Phase I After completing the preclinical trials now 120 volunteered are recruited for
GX-19 DNA vaccine
the initiation of phase I clinical trials. [4]
Acuitas Therapeutics (Vancouver) in collaboration with Imperial College
(London) developed a self-amplifying RNA (saRNA) lipid nanoparticle
encapsulated with the pre-fusion stabilized SARS-CoV-2 S protein.
They are characterized
Phase I
LNP-nCoVsaRNA mRNA vaccine for both the humoral and cellular immune response, as well as the
neutralization capacity of a pseudo-typed SARS-CoV-2. The mice were
immunized with two injections, one month apart, at specific doses ranging
from 0.01 μg to 10 μg. After 6 weeks, robust SARS-CoV-2 S protein-specific
IgG antibodies were seen in animals in a dose-dependent manner. 33
After the preclinical trial the vaccine has secured confirmation from the
LNPCureVac German Health Authority Paul-Ehrlich-Institute (PEI) and Belgian Federal
mRNA vaccine Phase II
- CVnCoV Agency for Medicines and Health Products (FAMHP) for the conduction of
phase I clinical trials. 12
After the preclinical trials, then phase I trials started June 29 2020 with 30
healthy volunteers aged 20-65. The trial is conducted in Osaka, Japan. Then
after the phase II trials started on August 31 2020 with 30 healthy volunteers
AG0302-COVID19 DNA Plasmid Phase III
aged 20-65. The trials are conducted in Osaka, Japan. After that phase III
trials are initiated on November 23 2020 with 500 healthy volunteers aged
above 18. The trials are going on in Japan.
CONCLUSION still under preclinical and clinical evaluation now, new

vaccines using nanotechnology also are on the race of
The recent outbreak of the COVID-19 virus causes huge
coronavirus vaccine trials. The scope of nanotechnology-
destruction to all or any of the continents around the world
based vaccines is going to be determined by the outcomes
claiming thousands of lives by the disease. So, there's an
of ongoing clinical trials.
urgent got to develop an efficient therapeutic strategy to
save lots of many lives. Although researchers and scientists Nanotechnology-based mRNA, DNA, and recombinant
from universities and corporations from everywhere the protein vaccine offer large advantages like they will be
planet are put considerable efforts to seek out a cure for delivered into the targeted host cells to create immunity
COVID-19 no specific therapy has been identified. While against the coronavirus wouldn't are feasible without
several vaccines made by conventional technologies are nanoparticles as a delivery vehicle. Nanoparticles also

provide the solutions to deal with the unmet delivery 1798–801.

challenges related to the utilization of naked DNA plasmids 12. Chauhan G, Madou MJ, Kalra S, Chopra V, Ghosh D,
or mRNA for vaccine development. Such solutions provide Martinez-Chapa SO. Nanotechnology for COVID-19:
the power to deliver DNA plasmids or mRNA vaccines in Therapeutics and Vaccine Research. ACS Nano. 2020; 14(7):
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the traditional vaccine approaches (e.g., inactivated and Delivery in Cancer Immunotherapy. ACS Nano. 2017; 11(3):
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potential to be a crucial tool for tackling the COVID-19 14. Since January 2020 Elsevier has created a COVID-19 resource
outbreak and will be a crucial technology to prevent future centre with free information in English and Mandarin on the
disease outbreaks. novel coronavirus COVID- 19 . The COVID-19 resource centre
is hosted on Elsevier Connect , the company ’ s public news
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A Pervasive Review on New Advancements of Nano Vaccines on Covid-19

Ranajit Nath Ambika Mandal

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A Pervasive Review on New Advancements of Nano Vaccines on Covid-19 Pandamic

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Received: 18-07-2021; Revised: 23-09-2021; Accepted: 30-09-2021; Published on: 15-10-2021.

The three months from the date of 30th January 2020,

T he novel coronavirus which is now officially declared

International Journal of Pharmaceutical Sciences Review and Research

▪ Ability to create active targeting Table 1: Characteristics of nanocarriers as nano vaccines 20

International Journal of Pharmaceutical Sciences Review and Research

▪ Small-molecule drug-based therapies nanomaterial to induce complimenting immuno-

upregulate robust T and B cell priming by releasing Protein sub-unit vaccine

International Journal of Pharmaceutical Sciences Review and Research

International Journal of Pharmaceutical Sciences Review and Research

International Journal of Pharmaceutical Sciences Review and Research

International Journal of Pharmaceutical Sciences Review and Research

International Journal of Pharmaceutical Sciences Review and Research

Table 2: List of Nano vaccines under clinical trial

CONCLUSION still under preclinical and clinical evaluation now, new

International Journal of Pharmaceutical Sciences Review and Research

provide the solutions to deal with the unmet delivery 1798–801.

International Journal of Pharmaceutical Sciences Review and Research

International Journal of Pharmaceutical Sciences Review and Research

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