COVID-19 / Vaccine / Health
The Science Behind the Covid-19 Vaccination Under Investigation
Several experimental vaccines targeting COVID-19 are currently in clinical trials. Moderna, the maker of the vaccine mRNA-1273 says that their vaccine against the novel coronavirus COVID-19 may be available this fall to a select group of people.
Phase 1 trials of mRNA-1273 began earlier this month. This experimental vaccine targets proteins on the outer structure of coronavirus. The vaccine works by introducing synthetic mRNA sequences into patients. These molecules allow for the host system to translate them into proteins that mimic those found on COVID-19. These proteins then circulate within patients and elicit an immune response that researchers hope will induce immunity to COVID-19.
Injecting mRNA vaccines to generate protein expression is a difficult process simply because it goes against the body’s natural biology. In the cell, mRNA serves as an intermediate between the code written into the cell’s DNA and the ultimate protein that it will create. mRNA is made within the nucleus of the cell, and as it matures it travels into the cytoplasm (the space between the nucleus and the outer plasma membrane) where it is translated into proteins by the cells ribosomes. mRNA is generally only stable within the cell long enough for proteins to be translated, and is soon thereafter degraded.
These vaccines require that mRNA be introduced into the cytoplasm from outside the cell — directly violating the central dogma of biology. In fact, genetic material of any kind that is introduced from outside of the cell is generally treated as a foreign invader and degraded rapidly. This poses a difficult challenge to the efficacy of the mRNA-1273 vaccine.
Derreck Rossi of the Harvard Stem Cell Institute and co-founder of Moderna has figured out a way to enhance the stability of mRNA molecules introduce into the cell. RNA is a polymer of just 4 basic molecules known as nucleotides — adenine, guanine, cytosine and uracil (A,G,C,U) — linked in succession. Rossi’s team found that by modifying two of these molecules, he could enhance the stability of the molecule. One change he made was to replace uracil with pseudouracil. This simple change allowed mRNA introduced from outside of the cell to evade degradation long enough to express their coded proteins (Rossi D, 2010).
Another issue facing mRNA vaccines is shuttling the mRNA across the outer cell membrane. The plasma membrane acts much like the skin of the cell, selectively deciding which molecules can cross into or out of the cell and which cannot. mRNA molecules can not readily cross the plasma membrane, thus mRNA vaccines would need a little help. Technologies exist that link vaccine mRNA with molecules than allow them to enter the cell. These can include molecules like protamines, lipids and nanoparticles (Kaufmann K, 2016) all of which address make them more permeable, or allow for them to be facilitated into the cell (Kaufmann K, 2016).
Results of phase 1 trials for mRNA-1273 are still a few weeks out, but the team feels hopeful that they will be able to release the vaccine in limited supply.
Who Would Get The Vaccine?
Should trials be successful, the earlier than expected release of mRNA-1273 would be administered in limited fashion, likely only to health care providers. These authorizations would potentially come under the FDA Emergency Use Authorization, which fast tracks medical treatment, testing and equipment in the case of emergency.
The experimental vaccine mRNA-1273 is still awaiting results of it’s phase 1 clinical trial currently underway in Washington State. More information on these trials can be found here.
Kaufman K, 2016: https://doi.org/10.1016/j.jconrel.2015.12.032
Rossi D, 2010: https://doi.org/10.1016/j.stem.2010.08.012