Are the COVID-19 mRNA vaccines the culmination of a journey, or just a stepping stone?

by Matt Wheeler |

At the time of writing, at the end of November 2021, COVID-19 continues to dominate the headlines, and everyone’s lives. The vaccine booster program continues apace in the UK, with urgency growing following the discovery of a concerning new variant, Omicron. The coming weeks will determine how much of a roadblock this new heavily mutated version of the virus is likely to be.

It’s not always easy to say whether the pandemic era (so far) has gone by in a flash, or felt like forever – it’s realistically a personal feeling determined by all sorts of factors. However, what is indisputable is the unprecedented speed of the development and roll-out of the COVID-19 vaccines.

It’s probably pretty safe to say that most people had never heard of messenger RNA (mRNA) before Pfizer/BioNTech and Moderna were thrust into the limelight in 2020 – in essence, it is genetic material that tells the body how to make proteins. There seems to be a misconception amongst some that this vaccine technology is brand new and developed at breakneck pace; however, mRNA vaccines have a storied history of development.

The question is – is this moment the triumphant culmination of the mRNA story (spoiler: almost certainly not) or an important milestone on the way to further innovation?

First, let’s take a brief look back at the history of mRNA vaccines. The path to success was not direct; for many years, mRNA was considered unsuitable for use as a drug or vaccine, due to its instability and cost. It was discovered in the 1960s, and, in 1978, fatty membrane structures called liposomes were used to transport mRNA into mouse and human cells, to deliver genetic material into cells and induce protein expression – the basis of the technique that would later see code for the COVID ‘spike protein’ delivered via vaccine to spark an immune response.

Investment and scientific innovation by hundreds of researchers in the decades since, including chemically modified RNA and fine-tuning of the liposome delivery system, led to the approvals of the mRNA vaccines currently forming the backbone of the global response to COVID-19.

mRNA vaccines have a number of potential benefits, including the possibility of rapid development and progress into clinical trials, and the capability of adapting to new strains (this may soon be tested by the afore-mentioned Omicron variant – vaccine manufacturers are already claiming that new vaccines might be ready in 100 days if it proves to be resistant to the current jabs).

There is certainly growing confidence that mRNA vaccines could have far-reaching applications in other infectious diseases; not just combating other respiratory viruses, such as influenza, but also malaria (an mRNA vaccine candidate is currently being tested at Oxford’s Jenner Vaccine institute) and HIV – described as being in a ‘fifth decade of a global pandemic’.

Over twenty mRNA-based immunotherapies have entered clinical trials for cancers, with some promising results in solid tumour treatments. Most cancer vaccines are therapeutic rather than prophylactic (with the exception of those for virus-induced malignancies, such as HPV). They must efficiently express tumour antigens and elevate immunity. Early results have demonstrated the potential of mRNA vaccines in treatment of advanced melanoma.

Earlier this month, promising early stage results were reported for an mRNA-based therapeutic for heart failure – patients undergoing coronary artery bypass surgery had an mRNA-encoding vascular endothelial growth factor (VEGF-A) injected into the heart muscle, which is hoped to stimulate the repair and regeneration of the heart. Whilst more research is needed, there is potential for improving patient outcomes for heart failure, a chronic disease where half of patients die within five years of diagnosis.

It’s possible that mRNA technology could be refined still further. Self-amplifying mRNA vaccines encode a ‘replicase’ that enables amplification of the original strand of RNA in the cell, with the aim of much higher protein expression at lower doses. The path to mRNA vaccines has drawn on the work of hundreds of scientists and researchers over many decades. Their perseverance has already changed the course of a global pandemic, saving many lives – but it seems inevitable that there is far, far more to come. With technology that can be adapted at such pace, and with a perhaps unprecedented level of public scrutiny, clear and effective communication about mRNA vaccines and therapies will be vital.

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