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mRNA (Messenger ribonucleic acid): Disrupting the field of vaccinology

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26 March 2021

This innovative technology platform has the potential to revolutionise the vaccine development & manufacturing

Vaccinations have been helping to protect people from serious diseases for well over 100 years, so it can be easy to forget the cutting-edge technology involved in the fight against infectious diseases and protecting millions of lives each year.[1] At GSK, we have developed more than 40 vaccines, targeting every stage of life, and helping protect against 21 of the 32 diseases currently preventable by vaccination.  

The COVID-19 pandemic has accelerated the evolution in vaccinology and raised awareness of the value of vaccines. It has also validated a critical new technology that has the potential to significantly reduce discovery and development lead times of vaccines, and made their large-scale manufacturing faster and simpler. Despite the success of conventional vaccines, major challenges remain in developing vaccines against a variety of diseases, especially those caused by pathogens that are able to quickly evolve and evade the immune system. At GSK, we are investing in different approaches using messenger ribonucleic acid (mRNA), utilising its potential to provide benefits in different areas. mRNA is a biological molecule that is naturally produced in human cells and carries the genetic code for the cells in the body to produce proteins.

What is mRNA vaccine technology?

mRNA technology is a cutting-edge platform for the development of new vaccines and can potentially expand the range of diseases which can be prevented or treated by vaccines while also promising to significantly speed up development and manufacturing[2]. By using mRNA technology in vaccines, specific proteins (or antigens) can be produced by the body’s own cells, enabling the human immune system to mount a response resulting in prevention or fighting disease.[3] The mRNA vaccine technology has been validated after more than 30 years of research work through the rapid development and implementation throughout the COVID pandemic.



GSK is focusing on different mRNA approaches either through our collaboration with CureVac or in house, to enable multivalent and combination vaccines:

  • Optimised second-generation unmodified mRNA-based vaccines, focused on a COVID-19 vaccine targeting virus variants and five other infectious disease targets including flu
  • Modified mRNA, which would be potentially utilised to complement the non-modified mRNA constructs in GSK’s pipeline[5]
  • Self-amplifying mRNA (SAM) vaccines[6]


How does it work? 👇

mRNA is composed of different features that play an important role in regulating optimizing mRNA translation and stability and can be modified to increase stability and protein expression, and modulate immunogenicity and reactogenicity[7]. mRNA is then ‘packaged’ into a delivery vehicle called lipid nanoparticle that allows the mRNA to remain stable until it enters a cell in the body. Once the mRNA enters a cell, it is translated to produce a protein that will eventually trigger a protective immune response.  For instance, thanks to optimizations of the mRNA’s non-coding regions, the second-generation mRNA technology GSK is developing with CureVac has shown its potential to trigger significant and fast activation of immune responses in preclinical models [8].  SAM platform technology has the potential to facilitate a large amount of antigen production from an extremely small dose of vaccine and could trigger a sustained, or long-term immune response. Current research is looking at using this technology in a number of different areas.[9],[10] 

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Why is this important? 👇

Recent outbreaks of Ebola, Zika and COVID-19 have shown us that an accelerated and focused response is needed to address the rapid emergence of certain acute viral diseases.[11] Preclinical development of mRNA-based vaccines is potentially faster than conventional vaccines and it is also easier to quickly modify mRNA vaccines in the early stages of development in order to maximise efficacy or tailor them to different pathogens.[12]

Production of mRNA vaccines is potentially more flexible than conventional vaccines, allowing companies to repurpose facilities for vaccines against different pathogens or optimise vaccines for the same pathogen quickly, based on data from clinical trials. This could accelerate production by avoiding the historically longer time required to create purpose-built facilities to produce conventional vaccines.[13] However, mRNA technology is still an emerging platform compared to many established vaccine technologies and there may be unforeseen challenges in clinical use. It will therefore be vital to ensure multiple global sites are able to act quickly in the case of pandemic responses, while the essential production of conventional protein-based vaccines continues to ensure protection is available against other diseases.[10]

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Shaping the future of vaccine development

Innovation is the beating heart of our business – mRNA vaccine technology is one tool of a range we have in our vaccine toolbox. Applying our knowledge and expertise in vaccines over many decades, we are working to create new vaccines for many diseases that still threaten individuals, families, and communities around the world.

Rino Rappuoli, Chief Scientist Officer of Vaccines

While traditional methods of vaccine development have been effective for certain diseases and will continue to play a major role in the vaccine landscape in the future, not all diseases can be addressed with conventional vaccines. Advances in science and technology are helping us to better understand the genetic make-up of these diseases and create innovative vaccines where it wasn’t possible to develop them before.

Enhancing innovation through collaboration

One of the pillars of GSK Innovation strategy is to advance science and technology through collaborations with leading scientists, institutions, and companies around the world. Our agreement with CureVac complements our in-house work on mRNA vaccine development and offers great potential for scientific synergy in the area of mRNA-based vaccine technologies. Our access to multiple platforms will allow us to expand our ability to target different diseases with this breakthrough technology.

We believe scientific advances like mRNA vaccines and collaborations with leading experts and companies at the forefront of the scientific development will help us fight more diseases faster and more efficiently than ever before – allowing us to help improve the health of more people around the world.

References 

[1] https://www.who.int/health-topics/vaccines-and-immunization#tab=tab_1

[2] Pardi et al Nat Rev Drug Discov. 2018 Apr;17(4):261-279

[3] https://www.phgfoundation.org/briefing/rna-vaccines

[4] https://www.gsk.com/en-gb/media/press-releases/gsk-and-curevac-to-develop-next-generation-mrna-covid-19-vaccines/

[5] https://www.gsk.com/media/7050/gsk-investor-update_23-06-21.pdf

[6] https://www.gsk.com/en-gb/behind-the-science/innovation/gsk-s-sam-technology-could-revolutionise-vaccines/

[7] Nance and Meier. ACS Cent Sci. 2021;7:748−756; Linares-Fernández et al. Trends in Molecular Medicine. 2021;26(3):311-323

[8] Gebre et al all, Optimization of Non-Coding Regions Improves Protective Efficacy of an mRNA SARS-CoV-2 Vaccine in Nonhuman Primates – available: https://www.biorxiv.org/content/10.1101/2021.08.13.456316v1  or https://www.gsk.com/en-gb/media/press-releases/second-generation-mrna-covid-19-vaccine-candidate/

[9] Access to Medicines Foundation, Antimicrobial resistance 2018 benchmark.  Available at: https://accesstomedicinefoundation.org/media/uploads/downloads/5f292e3996b58_Antimicrobial-Resistance-Benchmark-2018.pdf

[10] https://www.gsk.com/en-gb/research-and-development/our-pipeline/?vaccines

[11] Rodrigues, C. M. C., Pinto, M. V., Sadarangani, M. &Plotkin, S. A. Whither vaccines? J. Infect. 74 (Suppl.1), S2–S9 (2017)

[12] Hekele et al Emerg Microbes Infect. 2013 Aug; 2(8): e52

[13] Pardi et al Nat Rev Drug Discov. 2018 Apr;17(4):261-279

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