Strategies of developing specific SARS-CoV-2 vaccine:
Some mRNA vaccines have been developed for SARS-CoV-2 (table 1.), they
encode stable form of S protein before its fusion to the host cell
membrane and depend mainly on a recent genetic technique which does not
involve viral culture in the laboratory but in the human body instead.
This method involves mRNA fragments that encode the viral proteins which
are then injected into the body, subsequently, the viral proteins are
presented by the antigen presenting cells to be recognized by T and B
lymphocytes to start the activation of the host antiviral immune
response(7). Currently, there are many candidate mRNA vaccines that have
been approved by WHO. Most of them are still in the pre-clinical stage
of study except an LNP-encapsulated mRNA vaccine developed by Moderna
company and is currently in the clinical evaluation stage, phase I
(100).
DNA vaccines reflect the new evolutionary path of vaccine production.
Genetic manipulation is used to generate the vaccinations produced
through recombinant DNA processing. Basically, the DNA which encodes the
target protein is inserted into the appropriate cell line or
microorganism by a plasmid or viral vector where the DNA is then
converted to a protein. Afterwards, the product is extracted by
purification technique(101). One of the advantages of DNA vaccines is
that it is easy to manufacture such plasmids in big amounts in addition
to the long-life immunity they could provide (102).
AZD1222 is a recent DNA vaccine under trial (formerly known as ChAdOx1
nCoV-19) that is using adenovirus vector and targeting SARS-COV-2 S
protein resulting in generation of humoral immune response with
production of immunoglobulins against the virus. Five hundred and 10
volunteers aged between 18 and 55 years old were enrolled in this
single-blind randomized clinical trial study which generated an
acceptable safety profile and promising immunogenicity (103).
Preclinical investigations have been done in animal models to test the
results and efficacy of another DNA vaccine and has shown good primary
outcomes, then it was proceeded to enter human clinical trial, phase I.
The vaccine with the name INO-4800 vaccine is involving 40 healthy
individuals who are receiving, each, 2 doses of the vaccine with 4 weeks
interval in between, then their antibody responses are assessed(104).
Other many candidate DNA vaccine are approved by WHO but they are still
in the preclinical phase of study.
Similarly, eleven SARS-CoV-2 protein subunit candidate vaccines are
approved by WHO, all of them are in the preclinical phase. Examples
include capsid-like particle AdaptVac, Drosophila S2 insect cell
expression system VLPs and peptide antigens formulated in lipid
nanoparticle formulation (100). Protein Subunit vaccines include some
epitopes of the virus usually produced through recombinant DNA
techniques or viral culture(105). One advantage of this type of vaccines
is the relatively fewer number of antigens, hence lower chance of
potential side effects. However, this low number of antigenic epitopes
could elicit weaker immune response but this disadvantage is treated by
conjugating such epitopes with adjuvant proteins to bypass this
weakness(106).
Additionally, many replicating and non-replicating viral vector
candidate vaccine are being tested for efficacy and safety. Replicating
viral vectors such as measles, influenza vector expressing RBD and
horsepox vector expressing S protein are in the preclinical experiments
phase while non replicating viral vectors such as adenovirus type 5
vector is proceeding to clinical trial phase I and II with favorable
initial results in the preclinical phase (100).
Another advanced strategy is the production of vaccines that are formed
of virus like particles (VLPs) such as parts of the viral surface
proteins. This is a complex procedure that involves processing these
particles into more immunogenic proteins that could initiate the host
antibody and cell mediated immunity(107). VLP vaccine expressing viral
RBD as well as plant derived VLP are being tested pre-clinically and
approved by WHO(100).
Inactivated viruses’ vaccines work through including the whole virus
which has been deactivated either chemically or physically. These
vaccines are more stable compared to other types of vaccines as they are
usually maintained in powder form, but unfortunately less effective and
more expensive due to its complicated production machinery(108). Three
inactivated virus candidate vaccines are in the clinical human trial
stage phase III and are approved by WHO(100).
Table 1. Summary of SARS-CoV-2 candidate vaccines proceeding to phase 3
of human clinical trials approved by WHO, August 13, 2020(109)