A technique using synthesised messenger RNA (mRNA) instead of lab-grown viral proteins could make vaccines cheaper, simpler, and faster to produce, enabling more rapid response to potentially pandemic strains.

Most vaccines use surface proteins from a virus to ‘train’ the immune system to recognise and destroy it. The viral proteins are generally grown either in fertilised hen eggs or in cell culture. This growth stage is unreliable though, and it can take many months to produce sufficient viral protein for millions of vaccine doses.

This study, published in Nature Biotechnology, instead used synthesised mRNA strands encoding a surface protein of the H1N1 flu virus. The mRNA was injected into animals’ skin cells, causing them to start producing the viral protein themselves. This provoked an immune response that proved able to protect mice, ferrets and pigs from later infection with otherwise lethal doses of the virus.

Similar methods have been developed previously using DNA rather than RNA, but with mixed results; possibly in part because DNA has to pass through two membrane barriers to get into the cell nucleus where it operates. RNA is theoretically more straightforward because it acts outside the nucleus, but had previously been thought too unstable for use in a vaccine. The technique in this study overcame this by tweaking the sequence of the mRNA to vastly increase its stability without altering the protein it encodes.

Some potential advantages of this approach are that pandemic-ready quantities of vaccine could be available within weeks since there is no need to grow the virus, that the vaccine does not need to be kept refrigerated to be viable, and that it eliminates risk of allergic reactions to the egg protein ovalbumin.

The study authors conclude that mRNA vaccines could address a substantial need for more optimal flu protection, and could also potentially be applied to vaccinations against a wide range of infective diseases.

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