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Figure
legends:
Figure 1. Infection Mechanism of SARS-CoV-2. The infection
mechanism of coronaviruses starts from attachment and entry. Binding and
viral entry via membrane infusion rely on interactions between the Spike
protein and its ACE2 receptor. Then, cleavage of S protein by a protease
enzyme (TMPRSS-2) facilitates the entry. Once enter the cell
successfully, the RNA from virus begins its translation and proteolysis.
The virus then synthesizes RNA via its RNA-dependent RNA polymerase.
Following replication and RNA synthesis, Structural proteins are
synthesized leading to completion of assembly and release of viral
particles. Following release, virus is ingested by
antigen-presenting-cell (APCs), which can activate T-helper cells via
viral peptide. And T-helper cells enable other immune response. B cells
produce antibodies that can block the virus from infecting cells. In
addition to this cellular immune response, cytotoxic T cells identify
and destroy virus-infected cells.
Figure 2. Four types of vaccines are used against coronaviruses
via immune response. Vaccines can be prophylactic or therapeutic in
clinical practice and are able to be broadly divided into virus vaccines
(weakened virus and inactivated virus), viral-vector vaccines
(replicating viral vector and non-replicating viral vector), nucleic
acid vaccines (DNA vaccines and RNA vaccines), and protein-based
vaccines (protein subunits and virus like particles), which rely on
different viruses or viral parts. 1. A virus is conventionally weakened
for a vaccine by being passed through animal or human cells until it
picks up mutations that make it less able to cause disease. However,
only under the precisely controlled and characterized conditions can
live attenuated (weakened virus) vaccines provide the required
protective immunity to avoid obvious disease symptoms in the host
animal. 2. In inactivated vaccines, the virus is rendered uninfectious
using chemicals, such as formaldehyde, or heat. Making them, however,
requires starting with large quantities of infectious virus. And
inactivated vaccines must be totally innocuous and non-infective.
Inactivated vaccines have certain restrictions on the way of
presentation, resulting in a limited immune response, which requires
adjuvants or immunostimulants to enhance the response. 3. DNA vaccines
are generated by inserting a gene encoding for the antigens into a
bacteria-derived plasmid, which needs to be controlled by
a
powerful promoter (in most cases a
CMV-promoter).
DNA vaccines can affect not only humoral immunity but also cellular
immunity.
The
limitation of DNA vaccines is lower immunogenicity profiles, which
impede the desired clinical application. 4. RNA vaccine is often encased
in a lipid coat so it can enter cells. The three major challenges in the
delivery of RNA vaccines is instability due to RNase-mediated
degradation and high molecular weight. 5. Replicating vaccines tend to
be safe and provoke a strong immune response. Ebola vaccine is an
example of a viral-vector vaccine that replicates within cells. 6. For
non-replicating vaccines, booster shots can be needed to induce
long-lasting immunity. 7. Protein subunit-based vaccines are typically
used via combined adjuvants or delivery systems to elicit a protective
effect, and most of them are focusing on the virus’s spike protein or a
key part of it called the receptor binding domain. 8. Virus like
particle (VLP) vaccines utilize empty virus shells for mimicking the
coronavirus structure, but they show non-infectious ability because they
lack genetic material. VLP vaccines can trigger a strong immune response
while can be difficult to manufacture.