A new way to make vaccines

For hundreds of years humans have triggered the immune system on purpose, in advance, to prepare it for deadly invaders. Smallpox, measles, typhoid, and today, Covid-19.

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We can trace the history of vaccination back to early days of smallpox inoculation – to China & India in the 1500s (maybe much earlier). They scratched matter from smallpox sores into the arms of people in an attempt to prevent future fatal infections. It was basic, but it was the start of a science saving millions of lives today. Over the years, vaccine technology has become more refined, and now, we have added one more way of making vaccines, using messenger RNA.

Information flow in the cell goes in one direction - from DNA to messenger RNA (mRNA) to protein. The genes in our DNA encode instructions to build the protein machines that make our cells function. DNA is the store of this information and is kept in a small compartment called the nucleus. The ribosomes, the cellular machinery that makes proteins, are found in the main part of the cell - the cytoplasm. Messenger RNA then is the intermediary, it is a temporary copy of genes from the DNA, which can move to the cytoplasm to be translated into a protein.

While previous vaccines have directly used dead or crippled virus or bacteria – or viral or bacterial proteins or toxins – to trigger an immune response, mRNA vaccines work on an elegant system of sending in a message containing instructions for the cell to make a specific protein. Once the cell makes this protein some of it is presented on the outside of its cell membrane for the scanning immune system cells to test. Once it is recognised as foreign it triggers an immune response – antibodies against the protein are created, meaning the immune system is primed and ready to go should infection ever occur.

When Pfizer BioNTech announced in November 2020 that their new mRNA vaccine against Covid-19 infection had shown success in its Phase 3 clinical trial it was certainly big news for a world gripped in a pandemic, but also a leap forward for this field of research. The Covid-19 vaccines made by Pfizer and Moderna are the first mRNA vaccines to be approved for public use.

Not that this was something researchers had developed within a few months. Decades of work has gone into mRNA vaccine technology, on top of the decades of other work that has allowed a true understanding of information flow in the cell, and has provided the sequencing technology we need to figure out what message to write.

Associated Professor James Ussher of the University of Otago explains the steps in the research that have got us to this place, and what the future of this exciting technology might be. 

Thanks to WeBanjo3 for allowing use of their song ‘Dawn Breaks’ in this episode to explain information flow in the cell.

To learn more:

• If you want to learn about the history of vacccination, this timeline is an excellent resource.
• The early reports of smallpox inoculation are discussed in this paper ‘The origins of inoculation’.
• This 2018 Nature summary is a good background to mRNA vaccine technology development.
• If you want to deep dive into the mRNA vaccine there is this well researched blog that describes each part of the code, and this post that goes into the details of the lipid nanoparticle.
• This episode deals with how the vaccine works in that first phase up to immune system alert. If you want to know more about how the immune system functions, you can listen to this Our Changing World episode from last year.