The world urgently needs a COVID-19 vaccine to pull us out of the current crisis. Historically,
the discovery of a new vaccine is a laborious process taking many years, even decades. We
do not have the time! There are several approaches to discovering
a new vaccine. A live attenuated virus vaccine is created by reducing the virulence of the
virus and rendering it harmless. This process requires multiple passages of the virus through
an animal or animal tissue--a slow process. A subunit vaccine uses a fragment of the virus,
for example the spike protein, to create an immune response. Creating a subunit vaccine
requires recombinant DNA technology to insert the appropriate gene into a vector and then
isolate the protein from the fermentation medium. Ramping up production can be slow.
But what if you could circumvent all these slow steps? What if the body could make its
own vaccine? This is the idea behind an RNA vaccine (also known as mRNA vaccine). Let
us see how this would work. In the case of SARS CoV-2, the virus that
causes COVID-19, the RNA was isolated and the viral genome was decoded early in the
epidemic, and then it was possible to deduce what RNA sequence codes for which protein,
the spike protein, for example. Then many copies of the RNA sequence are made using
RNA polymerase. So, great! all we have to do is to get the
RNA to a patient's cell and let the cellular machinery produce the viral protein which
will confer immunity, right? Well, no. There are some problems here. First, RNA is a large
and polar molecule and does not readily pass through cell membranes.
Secondly, the body has enzymes, call ribonucleases that are present in every tissue. Ribonucleases
exist for the sole purpose of destroying wandering bits of RNA. They exist for a reason: you
do not want plant or animal RNA getting inside your cells and making their proteins. For
an RNA vaccine to work, the viral RNA must be protected from ribonucleases.
Here comes nanotechnology to the rescue. Lipid nanoparticles are tiny bubbles about 80 to
200 nm around. They are formed with walls made of lipid bilayers with a water center.
Lipid nanoparticles can be created to encapsulate RNA and shield it from ribonucleases. The
lipid nanoparticles also allow passage through the cell membrane.
The lipid nanoparticles containing their RNA payload would then be delivered via syringe
into the muscle or under the skin. The nanoparticles are absorbed by the body
and taken up by an antigen presenting cell (for example, a dendritic cell or B cell)
through endocytosis. The membranes of the lipid bilayer and the endosome merge resulting
in the release of the RNA package. Next, the RNA is translated to viral protein and
is then cleaved into fragments by the proteasome. The protein fragments are further processed
by the endoplasmic reticulum to make MHC which is transported to the cell membrane.
CD8 positive T cells bind to MHC1 creating a memory of the viral antigen. This sets in
motion a series of events leading to the attack of infected cells and the production of antibodies
to the virus. The immune system is now ready to save the day in case of future viral infection.
Lipid nanoparticles offer other advantages for vaccine technology. For example, the lipid
nanoparticles can be decorated with ligands that allow targeting to certain cell types
such as antigen presenting cells. Adjuvants can be added to the interior of the lipid
nanoparticle to further boost the immune system's response to the vaccine.
Lipid nanoparticle technology can solve the challenging problem of RNA delivery to cells.
RNA vaccines have the potential for rapid production and scalable manufacturing. It
should be emphasized that no RNA vaccine has been approved for widespread use in patients
YET, but several vaccines are in clinical trials, and they have elicited antibodies
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