The basis of upcoming Pfizer and Moderna coronavirus vaccines. How it works? Pluses and minuses.
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Vaccines prepare the immune system, getting it ready to fight disease-causing organisms, called pathogens. A vaccine is introduced to the body to mimic infection, triggering the body to produce antibodies against the pathogen, but without causing the illness. Conventional vaccines usually contain a weakened or inactivated pathogen; or a piece of a protein produced by the pathogen, called an antigen.
RNA vaccines are a new generation of vaccines. Instead of the antigen itself, RNA vaccines contain a messenger RNA – mRNA – that encodes for the antigen. Once inside the body’s cells, the mRNA is translated into protein, the antigen, by the same process the cells use to make their own proteins. The antigen is then displayed on the cell surface where it is recognized by the immune system. From here, the sequence of events is similar to that of a conventional vaccine.
Some RNA vaccines also contain additional mRNA coding for an enzyme, which, after being translated in host cells, can generate multiple copies of the antigen-encoding mRNA. This essentially amplifies the production of antigen from a small amount of vaccine, making the vaccine more effective. These are called self-amplifying RNA vaccines.
RNA vaccines are easier and safer to produce than conventional vaccines. This is because mRNA molecules can be synthesized in a cell-free system using a DNA template with a sequence of the pathogen; while conventional vaccines usually require a more complicated and risk-prone process of growing large amounts of infectious pathogens in chicken eggs or other mammalian cells. Without the risks of being contaminated by infectious elements or allergens from egg cultures, RNA vaccines are also safer for patients.
Because protein synthesis occurs in the cytoplasm, RNA molecules do not need to enter the nucleus, so the possibility of them integrating into the host cell genome is low. RNA strands are usually degraded by cellular enzymes once the protein is made.
The relative simplicity of the production process makes it easier to standardize and scale, enabling rapid responses to emerging pandemics. Other advantages include lower production costs, and the ease of tweaking RNA sequences to adapt to rapidly-mutating pathogens.
On the minus side, it can be challenging to deliver mRNA effectively to the cells, since RNA sequences and secondary structures may be recognized and destroyed by the innate immune system as soon as they are administered intravenously. These limitations can be overcome by optimizing codons, using modified nucleosides to avoid recognition, and packaging RNA into protective nanoparticles.
Another disadvantage is that most RNA vaccines require uninterrupted refrigeration for transportation and storage, which can be a hurdle for vaccine distribution. Research is ongoing to engineer thermostable vaccines.
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