What’s the difference between a protein-based vaccine and an mRNA vaccine?

The recent COVID-19 pandemic has raised our awareness of the different types of vaccines available. Two types of vaccines that you might have heard of are protein-based vaccines and mRNA vaccines. But what do these mean, and what’s the difference?

Protein-based vaccines, also known as subunit or conjugate vaccines, have been around for decades, and are still widely used for diseases like hepatitis B, influenza and human papillomavirus (HPV).^1,2 If you’ve ever been vaccinated against any of these diseases, you’ve most likely had a protein-based vaccine. More recently, protein-based vaccines have been created to target COVID-19.¹ Currently, three of the eight vaccines approved for use against COVID-19 in the EU are protein-based vaccines.³

These vaccines use a specific molecule (called an antigen) from the virus or ‘pathogen’, which has been carefully chosen to produce an immune response and create antibodies.⁴ Worried about getting ill from the antigen in the vaccine? Don’t be – the use of recombinant antigens in modern protein-based vaccines provoke the body’s immune response without causing disease.² Plus, some protein-based vaccines now use proteins that have been created (genetically engineered) to mimic the protein from the pathogen (referred to as a recombinant protein).⁴ These vaccines are also non-infectious because they do not contain the genetic material the virus needs to replicate inside cells.^4,5

While protein-based vaccines deliver a virus-like protein (antigen) ready-made, directly to the immune system, mRNA vaccines deliver genetic material (created in a laboratory) that instructs the body's cells to produce the antigen, which in turn triggers an immune response.^6,7 mRNA vaccines do not contain any live virus and cannot cause infection.⁶

Compared to protein-based vaccines, mRNA vaccines are relatively new.⁸ While the first mRNA flu vaccine was tested on mice in the 1990s, it wasn’t until 2011 that the first mRNA vaccines were tested in humans.⁸ This delay was because the mRNA would be immediately degraded before it could be translated into the antigen protein – an issue that was solved by advances in vaccine nanotechnology, which helped protect the mRNA as it was delivered to the cell.⁸

The first mRNA vaccines to complete all stages of clinical trials and be licensed for use were for COVID-19.⁹

While protein-based vaccines and mRNA vaccines are created differently, they both go through the same rigorous testing and approvals process.⁶ Exciting scientific developments are also being made in both types of vaccine technology, which will hopefully allow us to have even more effective vaccines in the future.^5,8

If you have any questions about vaccines, please speak to your doctor or healthcare professional.