Sanofi is taking a two-pronged approach to vaccine development to help meet global public health needs during the coronavirus pandemic.
For over a century, vaccines have been a pillar of medical care. Every vaccine developed to date is based upon the same fundamental principle: by teaching our immune systems to recognize a pathogen and destroy it, we can help protect our bodies from infectious disease.
Sanofi scientists are building on this principle, using both proven and new technologies to develop vaccines against SARS-CoV-2, the coronavirus that causes COVID-19. Leading the company's medical team in combatting the virus is Rosalind Hollingsworth, Medical Franchise Head, Global Medical Affairs at Sanofi Pasteur in Pennsylvania, USA. We asked her to explain the science behind Sanofi’s two vaccine candidates and how they are designed to act in the body.
Show me, teach me
"You have to show the immune system what its target is first–and that can be a piece of the virus, one of its proteins, for example. One of the most important challenges in developing a vaccine that offers the best chance of protection is discovering and validating which protein to direct the immune system to,” explained Hollingsworth.
Scientists who make vaccines can use many different technologies to generate these target proteins (or "antigens") and train the body to recognize and attack them.
How Sanofi’s candidate COVID-19 recombinant protein vaccine is made
Sanofi’s candidate recombinant protein coronavirus vaccine, currently under development, uses the same technology as one of Sanofi’s seasonal influenza vaccines. The flu protein is simply switched to a protein from the surface of the SARS-CoV-2 virus–the spike protein. The spike protein is a key player in helping the coronavirus get into a person's cells, including those in the lungs.1 Here's how the process works:
Proteins are relatively stable molecules, so a candidate vaccine made of purified spike proteins can be stored at between 2°C and 8°C like other vaccines using this same technology.2 This is typical for most vaccines for other diseases like influenza and pediatric vaccines, among others.
mRNA vaccine gains momentum
Sanofi's proven method for producing a recombinant protein vaccine to help prevent seasonal influenza, and its evaluation for prevention of COVID-19 disease, is just one of many approaches that will be needed to mount a global defense against the SARS-CoV-2 virus.
"There may be no one-size-fits-all solution, so we are exploring two technologies. One of the most fascinating of these is an mRNA-based vaccine, which are relatively new in the field. If you want to understand how it works, you might need to dust off your high-school biology and remember how, in your cells, DNA has instructions that are read by RNA, which carries out those instructions to make proteins," said Hollingsworth.
Rather than producing spike proteins in the lab, messenger RNA (mRNA) vaccines are designed to produce the desired antigens using the body's own protein-making machinery.3 Messenger RNA vaccines deliver instructions directly to a person's cells. When the cell carries out those instructions, they make just enough spike protein to stimulate the immune system to launch a fleet of antibodies to help fight it.
Then, as with a recombinant protein vaccine, the immune system commits the spike protein to memory. That way, when the full SARS-CoV-2 virus enters the body, immune cells will recognize the spike protein and mount a defense.
“mRNA vaccines leverage our own cells’ infrastructure to produce the antigens needed to train the immune system, and that is a really cool approach, but as with anything that is new, and as with all new vaccines, we will be very careful to comprehensively evaluate safety,” said Hollingsworth. “Another challenge with mRNA vaccines is that RNA itself is a very active molecule–it is made to do things, deliver messages, move around–so it is less stable than most proteins. Because of that, it needs to be stored at ultra-low temperatures to slow it down and preserve its biochemical activity."
The requirement for ultra-cold storage4 could be a challenge for global vaccine distribution; discovering solutions to this challenge is an area of intense research at Sanofi and beyond.
Working with our partners at GSK on the protein-based adjuvanted vaccine, and Translate Bio for the mRNA vaccine, has allowed us to make the most of a phenomenal range of expertise and propel this crucial work forward.
Find out more
- Huang, Y., Yang, C., Xu, Xf. et al. Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19. Acta Pharmacol Sin 41, 1141–1149 (2020). https://doi.org/10.1038/s41401-020-0485-4
- Quadrivalent Influenza Vaccine Package Insert BLA STN 125285/419, accessed at https://www.fda.gov/media/123144/download on 30 November 2020.
- Xu S, Yang K, Li R, Zhang L. mRNA Vaccine Era-Mechanisms, Drug Platform and Clinical Prospection. International Journal of Molecular Sciences. 2020 Sep;21(18). DOI: 10.3390/ijms21186582
- Kaiser J. Temperature concerns could slow the rollout of new coronavirus vaccines. Science (2020);
doi:10.1126/science.abf7422. Accessed 7 December 2020 at https://www.sciencemag.org/news/2020/11/temperature-concerns-could-slow-rollout-new-coronavirus-vaccines