Comparison of DNA and RNA based vaccine
Vaccine: A preparation of killed microorganisms,
living attenuated organisms, or living fully virulent organisms that is
administered to produce or artificially increase immunity to a particular
disease.
DNA VACCINE:
DNA vaccines are third generation
vaccines. They contain DNA that codes for specific proteins (antigens) from a
pathogen. The DNA is injected into cells, whose "inner machinery"
uses the DNA to synthesize the proteins. Because these proteins are recognized
as foreign, when they are processed by the host cells and displayed on their
surface, the immune system is alerted, that triggers immune responses.
Construction: DNA vaccines are composed of bacterial plasmids.
The construction of bacterial plasmids with vaccine inserts is accomplished
using recombinant DNA technology. Once constructed, the vaccine plasmid
is transformed into bacteria, where bacterial growth produces multiple plasmid
copies. The plasmid DNA is then purified from the bacteria, by separating the
circular plasmid from the much larger bacterial DNA and other bacterial
impurities. This purifies DNA acts as the vaccine (AAM, 1996).
Mechanisms: A plasmid vector that expresses the protein of interest (e.g. viral protein) under the control of an appropriate promoter is injected into the skin or muscle of the host. After uptake of the plasmid, the protein is produced endogenously and intracellularly processed into small antigenic peptides by the host proteases. The peptides then enter the lumen of the
RNA Vaccine:
The direct vaccination with mRNA
molecules that encode a target antigen induces an immune response after uptake
by antigen-presenting cells. Typically, mRNA vaccines are synthetically
produced by an enzymatic process. This process requires a transient
intermediary called messenger RNA that carries the genetic information to the
cell machinery responsible for protein synthesis.
RNA vaccine technology.
An
RNA is injected in the body (left). This RNA encodes the information to produce
the antigen, which is a protein from a pathogen that will stimulate the immune
system. Inside the cells, the RNA is used to synthesize the antigen, which is
exposed to the cell surface (middle). Then, a subset of immune system cells
recognizes the antigen and trigger an immune response (direct response and
long-term memory) (right).
Comparison of DNA and RNA based vaccine
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DNA
VACCINE
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RNA VACCINE
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DNA is the molecule that contains the genetic information of
the organism. It is composed of a series of four building blocks, whose
sequence gives the instructions to fabricate proteins.
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DNA provide instruction to produce antigen.
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In vivo expression ensures protein more closely
resembles normal eukaryotic structure, with accompanying post-translational
modifications.
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DNA vaccines, in general, they have been found to elicit less of
an immune response than other types of vaccine.
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The reasons for this are not completely clear, but possible
explanations include inefficient delivery of DNA into human cells, the need
for DNA to cross both cell and nuclear membranes and be transcribed in the
nucleus in order to transfect a cell, low expression of DNA-sensing
machinery, and differing expression of nucleic acid sensing pattern
recognition receptors
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The nucleic acid vaccine platform is appealing because it allows
easy delivery of multiple antigens with one immunization and induces both
humoral and cellular immune responses, which makes tumor escape less likely.
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The relatively poor immunogenicity of DNA vaccines combined with
concerns about their potential for oncogenesis via integration into the host
genome has driven a shift away from DNA vaccines and towards RNA vaccines
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Delivery of DNA vaccine via gene gun, dosage, jet injection
and intramuscular injection.
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This process requires a transient intermediary called
messenger RNA that carries the genetic information to the cell machinery
responsible for protein synthesis
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RNA provide instruction to
produce antigen
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. RNA can thus be produced in vitro, i.e.
outside the cells, using a DNA template containing the sequence of a specific
antigen. Creating a RNA vaccine also requires some engineering of the RNA to
achieve a strong expression of the antigen.
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While injection of simple RNA can elicit an immune response,
RNAs in this form are prone to a rapid degradation.
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RNA vaccines are attractive because they retain the same
appealing characteristics as DNA vaccines but also offer some additional
benefits. Unlike DNA, RNA only needs to gain entry into the cytoplasm, where
translation occurs, in order to transfect a cell.
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Moreover, RNA cannot
integrate into the genome and therefore has no oncogenic potential. In
addition to in vitro transcription, RNA can also be isolated from a
limited tumor sample and amplified using techniques such as polymerase chain
reaction (PCR), yielding large amounts of patient-specific antigens .Finally,
RNA can act as an adjuvant by providing costimulatory signals, for example,
via toll-like receptors. For these reasons, there is a growing interest in the
research and development of RNA vaccines.
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Delivery of RNA vaccines via various routes, including
intramuscular, intradermal, subcutaneous, intravenous, intrasplenic,
intranodal, intratumoral, and intranasal methods.
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RNA vaccine could be effective against a wide range of
infectious diseases and cancer.
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Producing RNA vaccines is also less expensive than producing
the full antigen protein.
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Production of RNA-based vaccines is more rapid compared to
production of traditional vaccines. This rapid production could be a major
advantage in face of sudden pandemics.
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RNA-based vaccines may be effective against pandemics because
they also provide more flexibility to prevent or treat pathogens that are
rapidly evolving .For instance, influenza vaccines.
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RNA-based vaccines offer a comparatively simple and rapid
solution to unpredictable, rapidly evolving pathogens.
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One is that RNA-based vaccines appear to perform better than
DNA-based vaccines. Another is that they are also safer, as injection of RNA
presents no risk of disrupting the cell’s natural DNA sequence.
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