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Course: MS Biology Education
SARS-CoV-2 gets into the cell through recognition by the spike protein
present on the surface of the virus envelope of the angiotensin converting enzyme 2
(ACE2) receptors (Li et al, 2020; Romano et al, 2020). This recognition or binding
represents the initial step for virus entry into cells. After attachment, the human
transmembrane protease serine 2 (TMPRSS2) cleaves and activates the spike protein
in an event that allows SARS-CoV-2 to enter the cells by endocytosis or direct fusion
of the viral envelope with the host membrane (Romano et al, 2020). Once inside the
cell, the infecting RNA acts as a messenger RNA, which is then translated by host
ribosomes to produce the viral replicative enzymes, which generate new RNA
genomes and the mRNAs for the synthesis of the components necessary to assemble
the new viral particles (Romano et al, 2020). The SARS-CoV-2 uses the same cell
entry receptor, which is angiotensin converting enzyme 2, same as SARS-CoV
(Zhou et al, 2020).
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heterogeneous and dependent on multiple variables, including age, sex, ethnicity,
and comorbidities (Hodgson et al, 2021).
Variants
Variants of viruses occur when there is a change or mutation to the virus’s
genes (Bollinger & Ray, 2021). Bollinger & Ray (2021) added that it is the nature of
RNA viruses such as the coronavirus to evolve and change gradually. A mutation can
help the virus spread or sicken, many don’t have any effect at all, and some forms of
the virus emerge and then disappear (Joseph, 2020). Occasionally, a mutation will
give the virus a better chance of surviving and reproducing itself and will result in a
new population known as a new lineage (Cleveland, 2021). Some changes of the
virus may affect its properties, such as how easily it spreads, the associated disease
severity, or the performance of vaccines, therapeutic medicines, diagnostic tools, or
other public health and social measures (WHO, 2021).
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RNA viruses mutate faster than DNA viruses because the polymerases of most
RNA viruses lack 3’ exonuclease proofreading activity and hence are more error-
prone than those of DNA viruses (Sanjuan & Domingo, 2016). The exception to this
rule is provided by coronaviruses, a family of positive-strand RNA viruses encoding
a complex RNA-dependent RNA polymerase that has a 3’ exonuclease domain
(Haas, 2021). Haas (2021) added that coronaviruses have a slightly lower mutation
rate than many other RNA viruses because they can do some light genetic
proofreading. Each time a new copy is made, there’s a chance that an error, or
mutation, will occur. According to Weisblum’s et al (2020) research, the SARS-CoV-
2 can mutate its spike proteins to evade antibodies.
According to the Centers for Disease and Control Prevention (2021), the
Alpha (B.1.1.7), Beta (B.1.351, B.1.351.2, B.1.351.3), Delta (B.1.617.2, AY.1, AY.2,
AY.3), and Gamma (P.1, P.1.1, P.1.2) variants are classified as variants of concern.
The World Health Organization (2021) has assigned labels for key variants of SARS-
CoV-2, using letters of the Greek alphabet. Since scientific names can be difficult to
recall, this system makes things easier to understand and helps prevent misreporting.
It also can help eliminate stigmatizing and discriminatory labels that people often
use when they refer to variants by their places of origin. The Variant of Concern
indicates highest threat perception among other coronavirus variants along with
possibly increased transmissibility, infectivity, or resistance to vaccines (WHO,
2021)
The Beta variant is first detected in South Africa on May 2020. This variant
has multiple mutations in the spike protein, including K417N, E484K, N501Y
(CDC, 2021). In K417N mutation, the amino acid lysine (K) is replaced with
asparagine (N). In E484K mutation, glutamic acid (E) is replaced with lysine (K).
The E484K and K417N receptor binding domain mutations and mutations in the N-
terminal domain have been associated with neutralizing antibody escape (CDC,
2021). The E484K mutation could help the virus dodge a person's immune system
and may affect how well vaccines work (Roberts, 2021). As with the SARS-COV-2,
the risk is still highest for elderly people and those with significant underlying health
conditions (Roberts, 2021).
The Delta variant is first detected in India in October 2020. According to Liu
et al (2021) research, the Delta SARS-CoV-2 has efficiently outcompeted the Alpha
variant in human lung epithelial cells and primary human airway tissues. Also, Zhao
et al (2021), has estimated that the Delta variant is about twice as transmissible as
the virus from the initial outbreak. P681R spike mutation is responsible for increased
infectivity of the delta variant by increasing the dissociation of the spike S1 and S2
subunits at the furin cleavage site (Liu et al, 2021; Zhao et al, 2021). Zhao et al
(2021) concluded in their research that its infection has a shorter incubation period
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with a viral load of >1,000 times greater than that by earlier variants, but it remains
uncertain whether or not it can cause more severe disease (Zhao et al.). Liu et al
(2021) suggested in their study that spike mutations that potentially affect furin
cleavage efficiency must be closely monitored for future variant surveillance
COVID-19 Vaccine
The COVID-19 outbreak, that started in Wuhan, China, in December of 2019
spread rapidly around the world, and the WHO has declared it as a pandemic on
March 11, 2020. Because no reliable COVID-19 treatment has yet been established,
vaccination has become the focus of public attention. Vaccination against COVID-
19 is largely believed to be the only effective method to end the current pandemic.
Because COVID vaccines have only been developed in the past months, it’s too early
to know the duration of protection of COVID-19 vaccines (WHO, 2021). But
according to the data, it suggests that most people who recover from COVID-19
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develop an immune response that provides at least some period of protection against
reinfection (WHO, 2021).
Scientists around the world are developing many potential vaccines for
COVID-19. All COVID-19 vaccines approved by WHO for emergency use listing
have been through randomized clinical trials to test their quality, safety, and efficacy.
To be approved, vaccines are required to have a high efficacy rate of 50% or above
(WHO, 2021). After approval, they continue to be monitored for ongoing safety and
effectiveness. Vaccine efficacy is a measure of how much the vaccine lowered the
risk of getting sick in a controlled clinical trial, while vaccine effectiveness refers to
how the vaccine performs in the wider populations (WHO, 2021).
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There are many types of COVID-19 vaccine. These are messenger RNA based
vaccines, viral vectored vaccines, inactivated vaccines, and protein-based vaccines.
Messenger RNA based vaccines are Pfizer-BioNTech and Moderna, it works by
directly delivering the genetic information to the cell for expressing the spike protein
into the body and the expressed viral protein will induce immune responses (GVN,
2021). Viral vectored vaccines are AstraZeneca, and Johnson & Johnson, it works
by delivering and expressing the spike protein using other viruses (GVN, 2021).
Inactivated vaccines are Sinopharm, and Sinovac, are the classic vaccine approach,
because it uses a killed virus particles containing the spike protein but also all other
viral proteins (GVN, 2021). A protein-based vaccines is Novavax, which use
harmless fragments of proteins or protein shells that mimic the COVID-19 virus to
safely generate an immune response (WHO, 2021).
Pfizer
The Pfizer vaccine has been developed by an American corporation called
Pfizer in New York and BioNTech, a German biotechnology company based in
Mainz, Germany (Walsh, 2021). The Pfizer-BioNTech COVID-19 Vaccine will now
be marketed as Comirnaty. On December 11, 2020, the US FDA authorized the
emergency use of the Pfizer-BioNTech COVID-19 Vaccine to prevent COVID-19 in
individuals 16 of years and older. It was on August 23, 2021, that it was approved
by the FDA as the first COVID-19 vaccine. The vaccine continues to be available
under emergency use authorization, including for individuals 12 through 15 years of
age and for the administration of a third dose in certain immunocompromised
individuals. Its mode of action according to the Pfizer-BioNTech Fact Sheets (2021),
is the nucleoside-modified mRNA in Comirnaty is formulated in lipid particles,
which enable delivery of the mRNA into host cells to allow expression of the SARS-
CoV-2 S antigen. It uses an mRNA to provide a blueprint for the cells to build body’s
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defense against the virus and this allows the body to generate an antibody response,
and to retain the information in memory immune cells, with the goal of attacking the
virus if the vaccinated individual is exposed.
The vaccine is given as an injection into the muscle in a series of 2 doses given
3 weeks apart, and a third dose is given in certain immunocompromised individuals.
A single dose of Comirnaty contains 30 ug mRNA in a volume of 0.3 mL, and it
does not contain preservative. In an analysis presented by the Pfizer-BioNTech Fact
Sheets (2021) to support its use in individuals 16 years of age older, there are 36,523
participants in the ongoing randomized, blinded, placebo-controlled international
study, the majority of whom are U.S. participants, who completed the 2-dose
vaccination regimen and did not have evidence of SARS-CoV-2 infection through 7
days after the second dose. Among these participants, 18,198 received the vaccine
and 18,325 received saline placebo. The vaccine was reported to be 95 % effective
in preventing COVID-19 disease among these clinical trial participants. Data is not
yet available to inform about the duration of protection that the vaccine will provide.
A study conducted between July 27, 2020, and November 14, 2020 by Polack
et al (2020) measures the safety and efficacy of Pfizer vaccine on a total of 43,548
participants who underwent randomization in preventing Covid-19 in persons 16
years of age or older. The participants who underwent randomization are from
United States, Argentina, Brazil, South Africa, Germany, and Turkey. The safety
profile of Pfizer vaccine was characterized by short-term, mild-to-moderate pain at
the injection site, fatigue, and headache. They concluded that the two-dose regimen
of Pfizer vaccine, given 21 days apart offered a 95% protection against Covid-19 in
persons 16 years of age or older (Polack et al, 2020).
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Moderna
The Moderna COVID-19 vaccine or mRNA-1273 is sold under the brand
name Spikevax. The vaccine is developed by the Moderna is a US pharmaceutical
and biotechnology company in Cambridge, Massachusetts. The mRNA-
1273 vaccine is like Pfizer vaccine, an mRNA vaccine that sends the body’s cells
instructions for making a spike protein that will train the immune system to
recognize it. The immune system will then attack the spike protein the next time it
sees one. The vaccine is given as an injection into the muscle in a series of 2 doses,
.5ml each given 28 days apart. The Moderna vaccine has an efficacy of
approximately 94.1 % in protecting against COVID-19, starting 14 days after the
first dose (WHO, 2021). According to the World Health Organization (2021), the
new variants of SARS-CoV-2, including the Alpha and the Beta, do not alter its
effectiveness.
AstraZeneca
The ChAdOx1-S or AZD1222 or Oxford–AstraZeneca COVID-19 vaccine is
developed by Oxford University and AstraZeneca Pharmaceuticals. It was on 28
January 2021 that the FDA authorized its emergency use to prevent COVID-19 in
individuals 16 of years and older. The vaccine is composed of a single recombinant,
replication-deficient chimpanzee adenovirus vector encoding the S glycoprotein of
SARS- CoV-2 (FDA, 2021). Following administration, the S glycoprotein of SARS-
CoV-2 is expressed locally stimulating neutralizing antibody and cellular immune
responses. The recommended dosage is two doses given intramuscularly at .5 ml
each with an interval of 8 to 12 weeks. According to the World Health Organization
(2021), the AstraZeneca vaccine against COVID-19 has an efficacy of 63.09%
against symptomatic SARS-CoV-2 infection. Longer dose intervals within the 8 to
12 weeks range are associated with greater vaccine efficacy (WHO, 2021)
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A study conducted by Bernal et al. (2021), compared the effectiveness of
Pfizer vaccine and AstraZeneca vaccine against the Delta variant and the Alpha
variant against symptomatic sequenced cases of COVID-19 in England. They found
that a 2 dose of Pfizer vaccine effectiveness is 93.4% with Alpha and 87.9% with
Delta (Bernal et al, 2021). With AstraZeneca vaccine 2 dose effectiveness is 66.1%
with Alpha and 59.8% with Delta (Bernal et al, 2021). They concluded that
sequenced cases detected after 1 or 2 doses of vaccination had a higher odd of
infection with Delta compared to unvaccinated cases (Bernal et al, 2021).
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Sinovac
The private Chinese company Sinovac developed a coronavirus vaccine called
CoronaVac (Corum and Zimmer, 2021). It is a vaccine made from Coronaviruses.
To create CoronaVac, the Sinovac researchers started by obtaining samples of the
coronavirus from patients in China, Britain, Italy, Spain and Switzerland (Corum
and Zimmer, 2021). One sample from China eventually served as the basis for the
vaccine. According to the BBC News (2021), the CoronaVac works by using killed
viral particles to expose the body's immune system to the virus without risking a
serious disease response. This means part of the coronavirus' genetic code is injected
into the body, triggering the body to begin making viral proteins, but not the whole
virus, which is enough to train the immune system to attack. The Sinovac-CoronaVac
vaccine is given as an injection into the muscle in a series of 2 doses, given 2–4
weeks between the first and second dose.
A study was conducted from February 2 through May 1, 2021, in Chile that
measures the effectiveness of SARS-CoV-2 Vaccine and the cohort included
approximately 10 million persons (Jara et al 2021). Among persons who were fully
immunized, the adjusted vaccine effectiveness was 65.9% for the prevention of
Covid-19 and 87.5% for the prevention of hospitalization, 90.3% for the prevention
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of ICU admission, and 86.3% for the prevention of Covid-19–related death (Jara,
2021).
Novavax
The Novavax COVID-19 vaccine is codenamed NVX-CoV2373. The
Novavax Incorporated is an American vaccine development company headquartered
in Maryland, US, with an additional site in Uppsala, Sweden (Whitehead, 2021).
The vaccine is manufactured at Fujifilm Diosynth Biotechnologies in Stockton-on-
Tees in northeast England (Whitehead, 2021). The NVX-CoV2373 COVID-19
vaccine contains a full-length, prefusion spike protein made using recombinant
nanoparticle technology and a proprietary saponin-based Matrix-M™ adjuvant
(WHO, 2021). The purified protein is encoded by the genetic sequence of the SARS-
CoV-2 spike protein and is produced in insect cells (WHO, 2021). The saponin-based
Matrix-M adjuvant stimulate the entry of antigen-presenting cells into the injection
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site and enhancing antigen presentation in local lymph nodes, boosting immune
response, and helping an immunized person make antibodies against the virus
(Carlson and Lutmer, 2021).
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