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International Journal of Modern Review Article
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VACCINE STRATEGIES AGAINST COVID19: A REVIEW

*Riddhi Goswami, Subhrojyoti Ghosh, Tiyasa Bhuniya, Aritra Paul, Anuvab Dey, Madhurima Koley,
Souhardya Bandyopadhyay

Department of Biotechnology, Heritage Institute of Technology, Kolkata 700107.

Received on: 13/05/2022 ABSTRACT

Revised on: 03/06/2022
Severe Acute Respiratory Syndrome Corona Virus 2 (SARS CoV 2), belonging to the
Accepted on: 23/06/2022 Coronaviridae family, is the main cause of COVID 19. Being a positive single-
stranded virus, it spreads primarily through cough and sneeze and exerts its
*Corresponding Author downstream effects by binding to angiotensin-converting enzyme 2 (ACE 2)
Riddhi Goswami transmembrane protein that controls the renin - angiotensin system. During the
prolonged period of intense lockdown, scientists had been trying to devise various
Department of Biotechnology,
effective vaccine strategies against the virus. One of the most direct consequences of
Heritage Institute of these researches is the development of different types of vaccines like DNA vaccines,
Technology, Kolkata 700107. mRNA vaccines, Viral Vector Vaccines, Protein Subunit Vaccines, Live attenuated
vaccines, Inactivated vaccines, Virus-like particle vaccines just to name a few. Some
vaccines have claimed efficacies to be as high as 93.5% in case of COVIran vaccines
while others have claimed efficacies to be as low as 45%. Many of the internationally
acclaimed and approved vaccines have efficacies in the intermediate ranges of 60%-
70% like Oxford Astrazeneca vaccine and the Moderna Vaccine. Clinical trials have
been conducted on participants from various parts of the world and different countries
have approved various vaccines for emergency usages based on the clinical data. At
present, 2 mostly used vaccines in India are Covishield and Covaxin. Our review paper
takes into consideration the principal vaccines developed in India and in the rest of the
world along with their mode of action, the number of doses required, the storage
conditions along with claimed efficacy and clinical trial data. This vaccination strategy
must be accelerated as much as possible in order to achieve the goal of ‗Herd
Immunity‘ at the earliest.

KEYWORDS: COVID 19 vaccines, vaccination strategy, viral mutants, vaccination

dosage, efficacy, clinical trials.

INTRODUCTION and economic problems. At this moment, effective

vaccines are urgently needed to bring a check to this
Over the centuries, there have been various kinds of
situation and thus help bring the society back to
epidemics and pandemics that have affected both
normalcy. Notably, within a few weeks after the start of
mankind and its civilizations alike. The Babylon flu
the then COVID-19 epidemic in Wuhan, China, Chinese
epidemic around 1200 B.C. is considered to be the
scientists isolated the viral pathogen of the disease which
earliest recorded pandemic. Many other pandemics have
was later named as SARS-CoV-2 by the World Health
also occurred since then. Some of them include the
Organization or WHO and sequenced its genetic code
Bubonic Plague of Europe, caused by the bacterium
which is an RNA or Ribonucleic Acid and shared it with
Yersinia Pestis which was disastrous and catastrophic
the entire world. This initiated a neck-to-neck global
and almost turned the entire Europe into a hell during the
competition to develop a vaccine against the virus with
14th century and the Spanish Flu pandemic which
vaccine producers using novel technical paradigms and
occurred in 1918 and is said to have killed one-third of
next generation vaccine platforms, as well as classical
the world‘s population then. Though the ongoing Corona
vaccine technology to increase the rate of their
Virus Disease 2019 (COVID-19) pandemic is much less
production and subsequently win the ‗vaccine race‘.
fatal, it still has killed about 6.2 million people in the
Since then, many COVID-19 vaccines have been
world, as of now. This pandemic proves the persistence,
researched, developed, tested and evaluated at an
infectivity, and virulence of the Severe Acute
unprecedented speed. As of April 2022, many vaccines
Respiratory Syndrome Corona Virus 2 (SARS-CoV-2)
have been conditionally approved and others are close to
which is the pathogen of the disease. The disease is still
such approval.[1] Here in this review, we are going to
spreading relentlessly and causing many social, health
look at all the types of COVID-19 vaccines that are

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Riddhi et al. International Journal of Modern Pharmaceutical Research

available throughout the world. We will discuss the vaccine, efficacy is around 70% and can be stored at 2 to
mode of action of a particular type of vaccine, 80C for 6 months.[4] In April 2020, clinical trials for the
while shedding light on the manufacturer, dosage, COVID-19 vaccine began. The primary goals of the
efficacy, clinical trials and authorizations of the vaccines Phase I, II, and III studies were to see if the ChAdOx1
in brief under a particular category. nCoV-19 vaccine would work against COVID-19, if it
would cause unacceptable side effects, and if it would
1. DNA Vaccine: DNA vaccination is a technique that induce good immune responses. Researchers looked
can be used against COVID19 by injecting genetically studied the immune response to vaccination in people of
engineered DNA to produce an immunological response. varied ages, to see if there is a difference in how
The mechanism involves fabrication of a circular double effectively the immune system reacts in elderly people or
stranded plasmid DNA encoding for the S protein of the youngsters.
pathogen. The steps of producing DNA Vaccine against
COVID19 are: inserting the genes to be expressed into 2.2 Janssen Vaccine: It has been manufactured by
the S protein of SARS CoV2 into plasmid vectors and Johnson and Johnson and 1 dose has been recommended.
expressing the genes in skeletal muscle cells or The vaccine can be stored at 2 to 8oC (3 months).[5]
adipocytes to facilitate an immune response. DNA According to the information provided by the
vaccine provides broad-based humoral, and cell mediated manufacturer, the Johnson & Johnson vaccine, or
immune response i.e., long lasting CTL response. Ad26.COV2.S, has been shown to be 66.9% effective in
a large-scale clinical investigation.[5] No information on
1.1 ZyCoV-D: It is the world‘s first indigenously phase I and II clinical trials is available. However, in
developed plasmid DNA vaccine manufactured by Zydus phase III, a primary analysis of a multicenter,
Life sciences Limited and Biotechnology Industry randomized, double-blind, placebo- controlled phase 3
Research Assistance Council. It carries the gene study was conducted in the United States, South Africa,
encoding SARS CoV2 spike protein, and its Brazil, Chile, Argentina, Colombia, Peru, and Mexico to
effectiveness has been increased by using it as an assess the efficacy, safety, and immunogenicity of a
intradermal injection with a spring-powered jet injector. single-dose of the Janssen COVID-19 Vaccine for the
3 doses have been recommended for this and the efficacy prevention of COVID-19 in adults aged 18 years and
is 66%.Clinical trials of phases 1 and 2 study revealed older (cut-off date January 22, 2021). The presence or
that the vaccine was safe, immunogenic and could be absence of comorbidities associated with a higher risk of
well tolerated. Phase 3 trial was a randomized, progression to severe COVID-19 were used to stratify
multicentered, placebo-controlled study to determine its the randomization. The demographic and baseline
efficacy, safety and immunogenicity. The study was characteristics of those who received the Janssen
carried out in more than 50 clinical sites throughout India COVID19 Vaccine and those who received placebo were
during second wave of COVID19, thus confirming the similar.[5] All 108 countries have approved this vaccine
vaccine‘s efficacy against new mutant variants, including India, Bangladesh and Afghanistan.[5]
especially the delta variant. It also showed that ZyCoV-D
is safe for 12-18 years children and has been authorized 2.3 Sputnik V: Russian company Panacea Biotech in
for emergency use in India and travel-only use in partnership with India's Serum Institute. The viral
Malaysia, New Zealand and Turkey. vectors in the Sputnik V COVID-19 vaccination are two
distinct adenoviruses. Adenovirus 26 (Ad26) is the viral
2. Viral Vector Vaccines: The mechanism involves vector in the first shot, while adenovirus 5 is the viral
inserting SARS CoV2‘s genetic material into a modified vector in the second shot (Ad5). The immune response is
form of a different virus which is used as a vector. When triggered by the SARS-CoV-2 spike protein gene, which
this viral vector enters the body, it distributes COVID19 is present in both injections.[6] The dosage is 2 doses and
virus‘s genetic information that instructs the cells to can be stored at -18.5oC (liquid form) and 2 to 8oC (dry
create copies of S protein. Human immune system form). Vaccine efficacy (VE) against moderate to
responds by producing antibodies and WBCs when the severeCOVID19 in adults 18 years of age and older was
cells exhibit the S protein on their surfaces to protect 66.9% at least 14 days after vaccination and 66.1% least
them from recurrence of the viral infection.[2] 28 days after vaccination in individuals who were
seronegative or had an unknown serostatus at baseline in
2.1 Oxford AstraZeneca Vaccine: The ChaAdOx1 individuals who were seronegative or had an unknown
vaccine was developed by Oxford University in serum.[7] Exploratory subgroup analyses of immunization
partnership with AstraZeneca and has been introduced in effectiveness against moderate to severeCOVID-19 were
India as Covishield vaccine by Serum Institute in Pune, conducted in Brazil, South Africa, and the United States.
Maharashtra. SARS CoV2 DNA has been inserted into a The subgroup analyses included all COVID- 19 patients
modified form of the Chimpanzee Adenovirus vector who had accumulated data up to the primary
AZD1222 and administered to humans. The DNA is effectiveness study data cut-off date, including cases
transcribed into RNA, which is then translated into Spike verified by the central laboratory and cases with a
proteins, which attract antibodies and cause an immune reported positive SARS-CoV-2 PCR from a local
response.[3] 2 doses have been recommended for this laboratory pending confirmation by the central

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Riddhi et al. International Journal of Modern Pharmaceutical Research

laboratory. Up until the data cut-off date, the PCR results production. Examples are UV treatment,[10] heat,[11]
from the local lab and the central lab were 90.3% in gamma irradiation,[12,13] psoralens.[14] hydrogen
agreement.[7] The vaccine went through all levels of pre- [15]
peroxide. and many more. Though only formaldehyde
clinical testing before entering clinical trials, including and β-Propiolactone (BPL) have been widely used for
research on a range of animals, including two species of inactivation of licensed human viral vaccines for
primates. On August 1, 2020, the vaccine‘s phase 1 and 2 decades.[9] Inactivation of a virus destroys its genetic
clinical trials were completed. There were no unexpected material which stops it from replicating. Inactivated
or unfavorable side effects for any of the individuals. vaccines can trigger immune response but that is not as
The vaccine elicited strong antibody and cellular strong as live attenuated virus vaccines. Therefore,
immunological responses. None of the subjects in the booster doses are needed to ensure ongoing protection.
current clinical trials became infected with COVID- 19
after receiving the vaccine. The vaccine has been 3.1 Sinopharm BIBP COVID-19 Vaccine: The
authorized in Russia, Belarus, Argentina, Bolivia, Serbia, COVID-19 vaccine BIBP, is an aluminum hydroxide-
Algeria, Palestine, Venezuela, Paraguay, Turkmenistan, adjuvanted, inactivated whole virus vaccine developed
Hungary, UAE, Iran, Republic of Guinea, Tunisia, by Sinopharm‘s Beijing Institute of Biological Products
Armenia, Mexico, Nicaragua, Lebanon, Myanmar, in China. The trade name of the vaccine is Covilo and is
Pakistan, Mongolia, Bahrain etc. India is the 70th country also known as BBIBP-CorV.[16] The WHO Strategic
to approve this vaccine.[7] Advisory Group of Experts (SAGE) has recommended
the use of BIBP vaccine as 2 doses of 0.5 ml given
2.4 Sputnik Light: Panacea Biotech Company in Russia, intramuscularly. Also, an additional dose should be
in partnership with India's Serum Institute. The first offered to persons aged 60 and above and persons who
component of Sputnik V, the world's first licensed are severe or moderately immunocompromised, as part
coronavirus vaccine, is Sputnik Light (recombinant of an extension of the primary series.[16] WHO has
human adenovirus serotype number 26 (rAd26). Sputnik recommended an interval of 3–4 weeks between the first
Light, like Sputnik V, is built on a well-studied human and second dose of primary series? A large international
adenovirus vector platform; these vectors cause the phase III trial has shown that 2 doses of BIBP
common cold and have coexisted peacefully with VACCINE, administered at an interval of 21 days, have
humans for millennia.[7] The dosage and storage an efficacy of 79% against symptomatic SARS-CoV-2
conditions of this vaccine are same as that of Sputnik V. infection, after 14 days or more from the second dose.
Sputnik Light is a one-shot vaccination that is both safe Vaccine efficacy against hospitalization was 79%.[17] A
and effective. As a stand-alone vaccination, Sputnik large multi-country (conducted in Bahrain, Egypt, Jordan
Light is very effective against Delta and other mutations. and United Arab Emirates) double blind, randomized,
The effectiveness of Sputnik Light as a booster will be phase III clinical trial, designed by the Wuhan Institute
comparable to that of two Sputnik V blasts against Delta. of Biological Products Co, Ltd, and the Beijing Institute
Efficacy was found to be around 80%.[7] The clinical trial of Biological Products Co, Ltd, both of which belong to
data of Sputnik Light is same as that of Sputnik V as per the China National Biotec Group Company Limited
the official website.[7] (CNBG), was performed on a large number of
participants. As of April 10, 2022, the Sinopharm BIBP
3. Inactivated Vaccines: Inactivated COVID-19 COVID-19 vaccine is authorized in 90 countries
vaccines contain SARS-CoV-2, which is either killed or including Algeria, Argentina, Bolivia, Brazil,
modified in such a way that it is unable to replicate Bangladesh, Cambodia, China, Egypt, and United Arab
within the host body. Due to the presence of the whole Emirates. WHO added the vaccine to the list of vaccines
virus along with its multiple surface antigenic authorized for emergency use for COVID-19 Vaccines
components, these vaccines induce a diverse Global Access (COVAX) ON 7 May 2021.[18] UK and
immunogenic response.[9] In this way immunization with Australia also approved and authorized it for
inactivated pathogens can provide protection against international visitors.
infectious diseases like COVID-19. Inactivated vaccines
have a higher safety profile as compared to the live 3.2 Covaxin: Covaxin (codenamed as BBV152) is
attenuated vaccines because they are less reactogenic and developed by Bharat Biotech of India in collaboration
give rise to a weaker immune response and are, with the Indian Council of Medical Research (ICMR) -
therefore, suitable for those with a compromised immune National Institute of Virology (NIV). It is a whole virion
system. They have a similar method of production like inactivated SARS-CoV-2 vaccine formulated with an
all other inactivated vaccines in which viruses are first imidazoquinolinone(IMDG) class molecule adsorbed to
cultivated on a suitable substrate for production of large alum.[19] SAGE recommended use of Covaxin as a 2-
amounts of antigen. Once propagated the viruses are dose series, 4 weeks apart, into the deltoid muscle of the
purified and concentrated prior to inactivation. Then they upper arm.A booster dose may be offered 4-6 months
are inactivated using physical or chemical methods or after completing the primary series for the highest- risk
combination of these two.[9] A wide range of well- groups, for example, older adults, health workers or
established inactivation agents or methods have been persons with comorbidities.[20] From phase III trial, the
proven successful to inactivate viruses for vaccine vaccine efficacy was found to be 78% against severe

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Riddhi et al. International Journal of Modern Pharmaceutical Research

COVID19 disease. For those with severe COVID-19, stabilized prefusion form of SARS-CoV-2 spike(S)
infected with a non-Delta variant of SARS CoV-2 virus, protein encapsulated in a lipid nanoparticle (LNP) vector
the vaccine efficacy was 84%. Also, efficiency of the that enhances uptake by the host immune cells.[34] This
vaccine against asymptomatic COVID-19 was 64%.[21] A LNPs acts as adjuvants and induce B-cell and T follicular
phase I trial was conducted on 375 adults which showed helper immune response. In this type of vaccine, mRNA
seroconversion rates of 92% in the 6 mcg with Algel- is directly inserted and in the host they are translated into
IMDG, 14 days after dose 2.[22] In phase II safety and target protein.[34] The overall design of mRNA contains
immunogenicity trial, conducted on 380 adolescent and an open reading frame (ORF) with a 3'-polyadenylated
adult participants neutralization response of the vaccine tail that induces cellular and humoral responses.[33]
was found significantly higher than phase I.[23] Phase III mRNA vaccines introduce a short-lived.[35] synthetically
trialwas conducted on 25798 participants, of whom created fragment of the RNA sequence of a virus into the
24419 were vaccinated with either 2 doses of Covaxin or individual being vaccinated. These mRNA fragments are
placebo. The participants were adults (≥18 years) among taken up by dendritic cells through phagocytosis.[36] The
whom 11% were aged >60 years, 33% were women and dendritic cells use their internal machinery (ribosomes)
28.6% had comorbidities. Primary analysis included the to read the mRNA and produce the viral antigens that the
vaccine efficacyto be 78%.[21] Covaxin received full mRNA encodes.[37] The body degrades the mRNA
authorization in India. The vaccine was also approved for fragments within a few days of introduction.[38] Although
emergency use in Iran, Zimbabwe, Nepal, Mexico, non-immune cells can potentially also absorb vaccine
Philippines, Guatemala, Nicaragua, Guyana, Venezuela mRNA, produce antigens, and display the antigens on
and Botswana. It was also approved in their surfaces, dendritic cells absorb the mRNA globules
Mauritius, Paraguay and Argentina. On 3 November much more readily.[39] The mRNA fragments are
2021, the World Health Organization (WHO) validated translated in the cytoplasm and do not affect the body's
the vaccine for emergency use.[24] but after a subsequent genomic DNA, located separately in the cell nucleus.[40]
inspection of manufacturing facilities WHO suspended
procurement of Covaxin through UN agencies in April 4.1 Pfizer-BioNTech COVID-19 Vaccine: It is sold
2022.[25] under the brand name of ―Comirnaty‖ it was
manufactured by Pfizer, of America in collaboration with
3.3 CoviVac Vaccine: The vaccine was manufactured BioNTech of Germany.[41] The vaccine usually delivered
by Chumakov Federal Scientific Center for Research and in vial once diluted contains 2.25 mL of vaccine,
Development of Immune and Biological Products, comprising 0.45 mL frozen and 1.8 mL of diluents. Each
Russia and was approved on 20th February, 2021.[26] The and every individual should be administered 0.3 mL of
CoviVac shot is given by intramuscular injection in two dose.[42] The initial course consists of two doses.[43] The
doses, 14 days apart and is recommended for use from 18 doses must be in an interval of three to four weeks. Later
to 60 years old.[27] One dose of 0.5 ml is composed only the interval of 12 weeks between two doses showed
of 3 μg or more of SARS-CoV-2 strain AYDAR-1 improved immunogenicity among patients. An additional
antigen inactivated by betapropiolactone and the 3rd or 4th dose can also be given in some countries
following excipients: 0.3–0.5 mg of aluminum hydroxide according to their requirement.[42] A test negative case
(adjuvant) 0.5 ml or less of phosphate buffer solution study published in august 2021 found duel doses
composed of disodium phosphate dihydrate, sodium of BNT162b2 had 93.7% effectiveness against
dihydrogen phosphate dihydrate, sodium chloride, and symptomatic disease caused by alpha variant and 88%
water for injection.[28] It is Russia‘s 3rd vaccine against against symptomatic delta variant.[44,45] In Preclinical
COVID-19 and has shown approximately 80% efficacy Trials, BNT162b1 and BNT162b2 emerged as strong
after preliminary trial results.[29] prospects based on the safety and immune response data
obtained and assessed on four BNT162RNA candidates.
The phase I /II trialsstarted on 21st September2020, and it In preclinical trials, the BNT162b1 and BNT162b2
continued till 15th October, 2020 [30]. Phase III trials vaccine candidates were given prophylactically to rhesus
started in early 2021 and are still ongoing and are macaques and mice, respectively. COVID-19 was not
expected to end on 30th December 2022 so efficacy has found in any of the animals that took part in the
not yet been established in Phase III trials.[31] Presently preclinical experiments. Two intramuscular (I.M.)
third (booster) dose of the anti-COVID vaccineCoviVac injections of 100 g BNT162b2 or 100 g saline were
is fully potent to enhance the immunity against novel given to macaques at random during the trial. On day 1,
coronavirus.[32] As the phase III trial is not complete so the first injection was administered, and on day 21, the
CoviVac is not fully authorized. On an emergency basis second injection was given. Macaques immunized with
it is authorized in Belarus, Cambodia, Russia and has 100 g of BNT162b2 had positive CD4+ and CD8+
travel permission only in Malaysia, New Zealand, responses, high levels of neutralizing antibodies, and
Turkey.[29] no signs of viral SARS-CoV-2 RNA or lung infection.[46]
In phase 1 and 2 Trial, between April 23, 2020, and May
4. mRNA Vaccines: mRNA vaccines contain mRNA 22, 2020, 60 healthy male and nonpregnant female
molecules that encode protein antigen.[33] The mRNA participants (96.7% Caucasian, one African American,
molecules contain informationfor the synthesis of and one Asian) between the ages of 18 and 55 years were

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Riddhi et al. International Journal of Modern Pharmaceutical Research

enrolled in phase 1/2 of the study in Germany. They (day 29 enzyme-linked immunosorbent assay anti–S-2P
were divided into 1 g, 10 g, 30 g, and 50 g dose groups. antibody geometric mean titer [GMT], 40,227 in the 25-g
In the beginning, each dose group had twelve group, 109,209 in the 100-g group, and 213,526 in the
participants who were injected intramuscularly on day 250g group). The titers increased after the second
1 and day 22. One participant from the 10 g dose group vaccination (day 57 GMT, 299,751, 782,719, and
and one participant from the 50 g dose group withdrew 1,192,154, respectively).[52] After phase 1 trial, the
from the trial due to unforeseen circumstances unrelated mRNA-1273 vaccine induced anti–SARS CoV-2
to the phase ½ clinical trials. Another group of twelve immune responses in all participants, and no trial-
participants in the 60 g dose group received only a limiting safety concerns were identified. The US Food
placebo. Mild to moderate side effects were observed in and Drug Administration has approved plans for a Phase
the 10 g and 30 g dose groups on day one, as II dosing and efficacy trial to begin in May.[50,53]
expected. Symptoms such as fever, chills, headache, joint Moderna began recruiting 600 adult participants for a
pain, muscle pain, and pain at the injection site were Phase II-a clinical trial on May 25, 2020, to assess the
common within 7 days of each vaccination. In both the safety and differences in antibody response to two doses
initial (day 1) and booster (day 22) immunizations, pain of its candidate vaccine, mRNA-1273. On July 27,
and tenderness at the injection site were common Moderna and the National Institute of Allergy and
complaints. There were no serious side effects in any of Infectious Diseases launched a Phase III trial in the
the dose groups, and thus no one dropped out of the United States, with the goal of enrolling and randomly
study due to serious side effects.[46] BNT162b2's Phase 3 assigning 30,000 volunteers to one of two groups: one
clinical trial began on July 27 and has so far enrolled receiving two 100-g doses of mRNA-1273 vaccine and
43,661 people, with 41,135 of them receiving a second the other receiving a 0.9 percent sodium chloride
dose of the vaccine candidate as of November 13, 2020. placebo.[54] Moderna had completed the enrollment of
Around42 percent of global participants and 30 percent 30,000 participants for its Phase III trial as of October
of U.S. participants come from racially and ethnically 2020.[55] The US National Institutes of Health announced
diverse backgrounds, and 41 percent of global and 45 on 15 November 2020, that overall trial results were
percent ofU.S. participants are between the ages of 56 positive.[56] Moderna vaccine got full authorization from
and 85, representing approximately 150 clinical trial sites 5 countries that include Australia, Canada, USA,
across the United States, Germany, Turkey, South Switzerland, United Kingdom and got emergency
Africa, Brazil, and Argentina. For the next two years, the authorization from almost 104 countries across the
trial will collect efficacy and safety data from world.[57]
participants.[47] Pfizer BioNTech vaccine got full
authorization from 10 countries that include Australia, 5. Virus-like Particle Vaccine: Virus-like particles are
Brazil, Canada, USA, Switzerland, Saudi-Arabia, Palau, the assemblies of supra- molecular particles.[58] They
New Zealand, Micronesia, Marshall Island and got consist of one or more than one viral proteins that are
emergency authorization from almost 140 countries self- assembled into various nanoparticles. They lack the
across the world.[48] pathogen‘s genetic material. VLP vaccines are a kind of
subunit vaccine which contains specific supra-molecular
4.2 Moderna Vaccine: Moderna COVID-19 vaccine, particles that are taken up by cells through non- specific
sold under the brand name Spikevax. developed by pathways such as phagocytosis and macropinocytosis.[59]
American company Moderna, the United States National VLPs are internalized into antigen presenting
Institute of Allergy and Infectious Diseases (NIAID), cells(APCs) , controlled within phagolysosome and the
and the Biomedical Advanced Research and resulting antigen peptides are presented to CD4 +helper T
Development Authority (BARDA).[49] Moderna cells by loading on MHC II molecules. Helper T cell
COVID19 vaccine is administered at an interval of 1 receptors identify epitopes presented on MHC II and
months in two doses each of 0.5 mL to 18 years old or activate themselves in additional signaling through
above. A third dose can also be given to 18 years old or costimulatory receptors and cytokines depending upon
above having undergone any organ transplant. A booster the strength of interaction. Because of their high
dose of 0.25 mL is eligible to be given to 18 years or stability, immunogenicity, diversity, and production
above after 5 months from the last dose administered.[50] versatility, VLPs are a promising technology for vaccine
The mRNA-1273 or moderna vaccine has a 94.1 percent design.[60] VLP technology offers an alternative platform
overall efficacy (89.3- 96.8). People between the ages of for developing effective vaccines against serious
18 and 65 have an efficacy of 95.6 percent (90.6-97.9), infectious diseases, and it is progressing in tandem with
while those over 65 have an efficacy of 86.4 percent mRNA and viral-vector-based vaccine.[61] VLPs are also
(61.4-95.2). This was discovered in a data analysis of far more immunogenic than other subunit vaccines
14134 candidates.[51] The Phase 1 trial began with an because they have repetitive antigenic epitopes on their
open-label trial in which 45 healthy adults aged 18 to 55 surface, which the immune system can detect.[62]
received two vaccinations with mRNA-1273 in doses of
25 g, 100 g, or 250 g, 28 days apart. Each dose group had 5.1 CoVLP Vaccine: CoVLP in the brand name of
a total of 15 participants. Antibody responses were Covifenz has been developed by Medicago of Canada
higher with higher doses following the first vaccination and GlaxoSmithK line.[63] It is authorized as a two-dose

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Riddhi et al. International Journal of Modern Pharmaceutical Research

regimen of 3.75 micrograms per dose, to be administered because they only contain a viral protein or group of
21 days apart.[64] A preliminary analysis by Medicago proteins, not the complete viral machinery needed for
and GSK on December 2021 found an overall efficacy of this virus to replicate. One disadvantage of this precision
71%, with 75% against the Delta variant and 89% vaccine is that the antigens used to elicit an immune
efficacy against Gamma variant.[64] In phase I results of response may lack pathogen-associated molecular
clinical trials, 180 adults (18–55 years) were randomized patterns, which are shared by a group of pathogens.
to receive two intramuscular doses of CoVLP (3.75 g,7.5 Immune cells can read these structures and
g, and 15 g) 21 days apart, either alone or adjuvanted recognize them as danger signals, so their absence could
with AS03 or CpG1018 at two sites in Quebec, Canada, result in a weakened immune response. Protein subunit
beginning in August 2020. All well-tolerated vaccines also elicit antibody-mediated immune responses
formulations and post-vaccination adverse events were because the antigens do not infect cells. This means that
mild to moderate, transient, and more common in the the immune response with this vaccine may be weaker
adjuvanted groups. There was no effect of CoVLP dose than with other vaccines. Protein subunit vaccines are
on serum NAbs, but both adjuvants significantly sometimes given with adjuvants (agents that stimulate
increased titers. NAbs in the CoVLP + AS03 groups the immune system) to overcome this problem, and
were more than tenfold higher than titers in Coronavirus booster doses may be required.[67]
2019 convalescent sera after the second dose. Cellular
responses to spike protein-specific interferon and 6.1 Nuxavoid: Nuvaxovid is a subunit COVID-19
interleukin-4 were also induced. This prespecified vaccine developed by the American Biotech company
interim analysis supports the CoVLP's further Novavax and the Coalition for Epidemic Preparedness
evaluation.[65,66] Medicago-GSK began a Phase II clinical Innovations (CEPI).[68] It is administered intramuscularly
trial for CoVLP with 588 participants in November 2020. as a course of 2 doses of 0.5 mL each. and is
Researchers published interim safety and recommended to administer the second dose 3 weeks
immunogenicity data from a Phase II, randomized, after the first dose in 18 years or above adults
placebo-controlled trial in adults aged 18 and up who (ema.europa.eu). The overall efficacy was 90.4% and
were immunized with a virus-like particle vaccine efficacy against moderate -to -severe disease was
candidate produced in plants displaying 19 SARS-CoV-2 100%.[69] On January 28, 2021, According to Novavax's
spike glycoprotein (CoVLP) adjuvanted with AS03 on report, preliminary results from its clinical trial in the
day 42. (NCT04636697). This report focused on United Kingdom showed that it was more than 89%
presenting safety, tolerability, and immunogenicity as effective.[70] The vaccine has an overall efficacy of 83.4
measured by 21 neutralizing antibody (NAb) and cell % two weeks after the first dose and 89.7% one week
mediated immunity (IFN- and IL-4 ELISpot) responses after the second dose, according to a primary Novavax-
in adults aged 18-64 (Adults) and Older Adults aged 65+ funded study published in The New England Journal of
(Older Adults) (Older Adults).[65,66] Medicago-GSK Medicine on June 30, 2021.[71] Phase I and II human
began a Phase III clinical trial for CoVLP in April 2021, trials Novavax's NVX-CoV2373, began in Melbourne on
enrolling 30,918 participants. (Medicago) CoVLP May 26, 2020. It enlisted the help of about 130
exhibited 69.5 percent efficacy against laboratory- volunteers, ranging in age from 18 to 59.[72] In December
confirmed, symptomatic SARS-CoV-2 infection starting 2021, Novavax announced that the vaccine had met its
at least 7 days after the second dose of the vaccine in the primary endpoint of preventing infection for at least
intention-to-treat analysis, even though the trial included seven days after the second dose in a phase III trial.
some participants who had previously been infected with Novavax began a pediatric expansion for the phase III
the virus when the trial began, according to the data clinical trial on May 3, 2021, with 3,000 adolescents
presented by Health Canada's National Advisory aged 12 to 17, yet no further documented report came
Committee on Immunization (NACI). In the per-protocol out.[73] Three countries have fully authorized this vaccine
analysis, it showed efficacy of 100.0 percent against the that include Australia, Canada & South Korea and almost
Alpha variant, 75.3 percent against the Delta variant, and 36 countries have given authorization for using it in
88.6 percent against the Gamma variant, with "similar" emergency situation.[74]
results in the intention-to-treat analysis.[64] The only
country to authorize this vaccine on 24th of February, to 6.2 Corbevax: It was developed by the Texas Children's
be used among 18-64 years old in Canada.[63] Hospital Center for Vaccine Development at Baylor
College of Medicine, in Texas. It was licensed to
6. Protein Subunit Vaccine: These are generated Biological E. Ltd.,of India, For production and further
through recombinant synthesis of protein antigens and development.[75] The vaccine is given using
purification method after cultivating large amounts of intramuscular injections in 2 doses, which are 28 days
pathogens. In case of COVID19 all protein subunit apart.0.5 ml of this vaccine is used for each dose.[76] nAB
vaccines target a specific viral protein called spike GMT against ancestral Wuhan strain indicates the
protein, one which seems to trigger a robust immune vaccine effectiveness of >90%. Vaccine effectiveness of
response. When the immune system encounters the >80% for the prevention of symptomatic infection is
spike protein it responds like it would as if seeing the indicated by the nABGMT against Delta strain. During
active virus itself. But this vaccine can‘t cause infection the continuous monitoring of the phase 2 trial, the

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Riddhi et al. International Journal of Modern Pharmaceutical Research

effectiveness of this vaccine was indicated by <30% drop Intramuscular injection of 0.5 ml is required in 2
of nAB GMT over a period of 6 months after the second individual doses(28 days apart). On the 56th day 0.5ml
dose.[76] Phase 1 study was uninterruptedly followed by of FINLAY-FR- 1A(Soberana Plus) can be given as a
Phase 2 study. Healthy volunteers from both the genders, booster dose. The 3 dose combination had a VE of
between ages 18 and 65(both inclusive) were enlisted for 92.4%, adjusted(CI 95% 86.9-95.6%). While the 2 dose
the trials.360 volunteers were there and they were schedule(without the booster dose) had an efficacy of
divided into random groups.4 formulations namely, 71.0%. Phase 3 trial was a double blind randomized trial
ECOV2D, BECOV2C, BECOV2B and BECOV2A were with 24,00 adults, aged between 18 and 80 years. They
introduced. Administration of the vaccine was performed were divided into vaccine and placebo groups in 4:1
via intramuscular injections, 28 days apart, with 0.5 ml ratio. They were further divided into 3 sub-groups. Sub-
of the vaccine in every dose. Registration ID is Group 1 received 25 µg of the vaccine in individual
CTRI/2020/11/029032.[77] Phase 2 trial was doses on day 0 and day 28. Sub group 2 received 25 µg
uninterruptedly followed by Phase 3 trial of the vaccine in individual doses on day 0 and day 28
(CTRI/2021/06/034014). Healthy volunteers from both and on the 56 th day received a booster dose of
the sexes, between ages 18 and 80 were enlisted for the SOBERANA PLUS along with the normal
trials. The total sample size was 1268. 0.5 ml of the dose. SOBERANA 02 is a conjugate vaccine so 25 µg of
vaccine was administered via intramuscular injections. 2 it contains RBD conjugated with Tetanus toxin. The
doses were administered, 28 days apart. Anti-RBD IgG Placebo group received 0.5 ml of Aluminium hydroxide
concentrations, neutralizing antibody titer, proportion of in a 3 dose regime (28th day and 56th day). The
candidates with solicited adverse reactions, SAEs and outcomes that were studied are-the effectiveness of the
MAAEs were checked during the trials at various vaccine in preventing symptomatic Covid-19 infection,
intervals. Safety follow up visits were performed humoral safety (under 2-dose + booster regimen), the
between 6-12 months after 2nd dose.[78] India has frequency of local and systemic events and mild,
approved this vaccine for emergency usage.[79] moderate, severe, critical adverse events and
death, cellular safety and SARS- CoV-2 virus
6.3 Soberana 02: Soberana 02 which has the technical neutralization assay. On June 29, 2021, Iran approved the
name of FINLAY FR-2 is produced by the Finlay use of SOBERANA 02 in an emergency. Cuba
Institute in Cuba and the Pasteur institute of Iran. authorized the emergency use of SOBERANA 02.[79]

Figure 1: Mode of action of all majorly available COVID-19 Vaccines: 1)Virus-like particles can be self
assembled in and released from recombinant yeast cells or other expression systems such as the vaccinia virus
expression system or even tobacco mosaic virus.2) Attenuated live pathogen vaccine strategies consist in
administering a debilitated form of live pathogen. Lengthy cell culture passaging in non-human cell lines or

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Riddhi et al. International Journal of Modern Pharmaceutical Research

animals decreases the virulence of the pathogen. This type of vaccines usually elicits robust and long-term
memory immune responses after a single dose.3) Inactivated pathogen vaccines contain whole pathogen that has
been submitted to heat or chemical treatment inactivation.4) Subunit vaccines are prepared either from antigen
purification of pathogens replicated in cell cultures or from recombinantly expressed antigens. These vaccines
commonly require adjuvant addition in order to deliver danger signals to antigen presenting cells and provoke
robust immune responses.5)mRNA vaccines are very quick to produce, yet were untested as successful human
vaccine strategies.6) Viral vector vaccines use a genetically manipulated measles or adenoviral platform to
express a foreign antigen commonly resulting in robust cellular and humoral response.7)Lastly, in DNA vaccines
the nucleic acid codifying for an immunogenic protein of the pathogen once administered is captured by antigen-
presenting cells that use it to express and present the antigen. These vaccines are predicted to have minor safety
issues as nucleic acid is swiftly degraded within the human body.

CONCLUSION https://www.janssencovid19vaccine.com/, (accessed

on 17th April 2022).
Since their approval, COVID-19 vaccines have protected
6. Medical News Today, ―How does Sputnik V
vaccinated individuals from the infection of COVID-19.
COVID Vaccine Work?‖, February 2021, Available
There are also data that strongly support the fact that
online:
certain vaccines can also prevent asymptomatic cases of
https://www.medicalnewstoday.com/articles/how-
COVID-19 in most instances. Despite such remarkable
does-the-sputnik-v-covid-19-vaccine-work
progress in COVID-19 vaccine development, there
(accessed on 17th April 2022.)
remain many questions that need to be answered. Though
7. Sputnik vaccine, ―Sputnik V-the first registered
clinical trial data shows that the approved COVID-19
COVID 19 Vaccine), June 2021, Available online:
vaccines are efficient, it is not yet known how long the
https://sputnikvaccine.com/, (accessed on 17th April
immunity will persist. A study predicts the decay of
2022.)
neutralization titre over the first 250 days after
8. Zhang J, Zeng H, Gu J et al.; Progress and Prospects
immunization with seven conditionally approved
on Vaccine Development against SARS-CoV-2.
vaccines although protection from severe diseases may
Vaccines (Basel), 2020 Mar 29; 8(2): 153. doi:
be retained. Finally, mutations of the S protein have been
10.3390/vaccines8020153. PMID: 32235387;
reported in the SARS-CoV-2 virus. The variants having
PMCID: PMC7349596.
these mutations may be more infectious and/or resistant
9. Budowsky EI, Bresler SE, Friedman EA et al.
to the neutralizing antibodies. Therefore, how mutations
Principles of selective inactivation of viral genome.
and its resultant.
I. UV-induced inactivation of influenza virus. Arch
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