In recent Journal of General Virology Scientists are debating the merits of moving the global flu vaccination system to a ribonucleic acid (mRNA)-based platform, as it could allow better control of the product and induce better immune responses. Scientists here also emphasize the possibility of developing a universal vaccine against the influenza virus.
Studies: A message in a bottle: mRNA influenza vaccination. Image credit: Mike Mareen / Shutterstock.com
Influenza vaccine research is an active area because these vaccines must be updated to account for ever-changing viruses, such as the recently discovered influenza A viruses (IAVs). Current influenza vaccines protect against both IAV and influenza B viruses (IBV) and are recommended to be administered annually because they are essential for controlling influenza pandemics. The three types of influenza vaccines currently include inactivated, live attenuated, and recombinant vaccines.
Vaccine efficacy may be reduced due to mismatch between vaccines and prevalent strains. Furthermore, in high-risk groups such as immunocompromised individuals and older adults, the immunogenicity of current vaccines is low. As a result, the World Health Organization (WHO) prioritizes the development of vaccines that induce stronger and longer-lasting immunity that are also safe and affordable.
One alternative approach is mRNA-based vaccines, which came to the fore during the coronavirus disease 2019 (COVID-19) pandemic. More specifically, both Moderna mRNA-1273 and Pfizer-BioNTech BNT162b2 are based on mRNA technology, where transcripts encoding the viral protein into cells are delivered by mRNA vaccines. The cells then use their machinery to synthesize and express these proteins, thereby mimicking the infection without actually using the infectious virus.
In 2012, researchers developed mRNA vaccines against multiple IAV subtypes that were immunogenic and protective against heterologous and matched challenges. Given the success of mRNA vaccines during the current pandemic, the development of a new generation of influenza vaccines should be carefully considered.
Production and distribution of mRNA vaccines
A vaccine platform, such as one based on mRNA technology, is required to enable faster formulation and deployment in the event of an influenza pandemic. There is also the potential benefit of finer geographic resolution for mRNA vaccines.
After developing a suitable mRNA template, the protein-coding region could be replaced, allowing for geographic customization. Tailoring vaccine deployment to specific regions would be easy with a faster production system that could potentially increase efficiency.
Immunogenicity of mRNA vaccines
Both the RNA and the delivery vehicle exhibit intrinsic immunogenicity. By triggering pattern recognition receptors in the cells, the synthetic RNA leads to the production of type one interferon (IFN).
In particular, mRNA can act as an adjuvant and consequently promote a strong immune response. However, the researchers cautioned that this property could also limit the development of safe and effective vaccines due to the targeted destruction and reactogenicity of mRNA before optimal translation.
Using manipulable determinants of immunogenicity, the mRNA platform provides a viable opportunity to extend the lifetime of the antigen present in the vaccine using self-amplifying mRNA vaccines. This method has already been used with many viruses, including SARS-CoV-2.
Commonly used influenza vaccines are non-adjuvanted; however, such vaccines are used in individuals 65 years of age or older. In addition, these vaccines could also help solve problems with recombinant vaccines.
Potential barriers and the future of mRNA vaccines
As observed with SARS-CoV-2, vaccination hesitancy and misinformation have led to significant uptake challenges in many countries, despite adequate vaccine supplies. In addition, selective vaccine uptake is likely to influence public perception of future mRNA formulations.
Influenza vaccines are unevenly distributed, with 95% going to Europe, the Americas and the Western Pacific in 2015; however, only 50% of the world’s population lives in these regions. These inequities should be remedied by developing a cheap, safe, rapid and easily portable vaccination system.
Nevertheless, issues related to adequate storage of mRNA vaccines must be addressed, as current influenza vaccines only need to be stored at 4°C. Ultimately, eliminating cold storage would help vaccine distribution in low-income and rural areas.
Link to journal:
- Shartouny, RJ & Lowen, CA (2022) Message in a bottle: mRNA influenza vaccination. Journal of General Virology 103(7). doi: 10.1099/jgv.0.001765.
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