An "overnight success" hundreds of years in the making- how the mRNA vaccines are connected to a huge "iceberg" of science

When we talk about the new mRNA vaccines it is important that we define what is NEW and what is the culmination of decades of research.

For example, the design of a mRNA construct for vaccination is actually decades old with a long research history.

What is new in the last 3-5 years research into how to efficiently utilize the translational machinery of the host cell to generate a antigen (part of a virus) presented appropriately to the immune system. This review goes through the long history of "systems biology in understand vaccines and how to target the immune system.

Overall we have a very detailed understanding about vaccines, the immune system.

General resources for understand the immune system

https://www.immunology.org/celebrate-vaccines/public-engagement/guide-childhood-vaccinations/how-vaccines-work

https://vk.ovg.ox.ac.uk/vk/how-do-vaccines-work

To the point where we have some really great video resources that use Normal language or ones that use medical terminology.


The name itself derives from the process of vaccination (originally using Cow pox (Vaccinia) to provide protection to Smallpox)


The core biology that mRNA-based therapeutics do not need to cross the nuclear envelope as opposed to DNA is an old concept from our basic understanding of gene expression. For at least two decades with have used the technique in cells and animal models to express proteins (mRNAs) in live cells.

However, the research showed what is necessary to reduce and side effects is brand new, e.g., double-stranded, RNA that activates innate immune sensors, thereby reducing protein expression. Similarly the idea that there is a receptor that recognizes parts of a virus- the Toll-Like Receptors (main resource). Mimicking virus with either co injected amino acids or ligands for immune cells up chance of appropriate immune response (review on TLR receptors)


More general context; that the new mRNA vaccines are the evolution of our understanding of inducing an efficient, safe immune response

Best reviews:

https://www.frontiersin.org/articles/10.3389/fimmu.2019.00594/full


https://www.nature.com/articles/s41541-020-0159-8


Furthermore, while it has been quicker than what we normally expect, researchers did a lot of testing.

The FDA/CDC have required (rightly) a full set of safety testing and this lead to a full set of protocols and guidance specific to each vaccine:


Pfizer testing for how handle, use and manage patient reactions:

https://www.cdc.gov/vaccines/covid-19/info-by-product/pfizer/index.html


Moderna

https://www.cdc.gov/vaccines/covid-19/info-by-product/moderna/index.html


What is facsinating to me is that we that the hope is that this new method and new use of old technology provides the breakthroughs needed to keep up in the "arms race" against diseases.


Fore more check out my Podcast Through a Scientist's Eyes: iTunes, Spotify, Google

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