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: What are they and how do they work?

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

mRNA vaccines: How are they different to protein-based vaccines?

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

Created differently, but tested and approved the same way

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

More information

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

Dirk Poelaert of Novavax
Dirk Poelaert, MD
Senior Director, Medical Affairs

Share this blog post on your social media.


  1. Marchese AM, et al. Vaccine. 2022;40:6567–6569.
  2. How Vaccines Work. Public Health 2023. Available at https://www.publichealth.org/public-awareness/understanding-vaccines/vaccines-work/ [Accessed 7 Sept 2021].
  3. COVID-19 medicines. Available at: https://www.ema.europa.eu/en/human-regulatory/overview/public-health-threats/coronavirus-disease-covid-19/covid-19-medicines#authorised-covid-19-treatments-section [Accessed 27 September]
  4. Vaccine Types. NIH 2019. Available at https://www.niaid.nih.gov/research/vaccine-types [Accessed 7 Sept 2021].
  5. Nascimento IP, Leite LCC. Braz J Med Biol Res. 2012;45:1102–1111.
  6. Understanding How COVID-19 Vaccines Work. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/how-they-work.html#:~:text=To%20trigger%20an%20immune%20response,immune%20response%20inside%20our%20bodies. [Accessed 27 September]
  7. Advances in COVID-19 mRNA vaccine development. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8940982/ {Accessed 27 September}
  8. The Long History of mRNA Vaccines. Johns Hopkins Bloomberg School of Public Health 2021. https://publichealth.jhu.edu/2021/the-long-history-of-mrna-vaccines#:~:text=There%27s%20a%20big%20gap%20between,tested%20in%20humans%20in%202013.[Accessed 7 Sept 2021].
  9. Five Things You Need to Know About: mRNA Vaccine Safety. European Commission 2020. https://ec.europa.eu/research-and-innovation/en/horizon-magazine/five-things-you-need-know-about-mrna-vaccine-safety [Accessed 7 Sept 2021].