WE ALL WAITED yesterday to see what advice the European Medicines Agency would give about the AstraZeneca vaccine. It’s been tough for everyone waiting for vaccine roll out in the midst of this most destructive of pandemics.
In all the news headlines about rollout, approval and efficacy, it is easy to forget just how far we have come and what science has achieved in relation to Covid. When we look back on the first half of the twentieth century, we see the time when mankind turned the tables on our bacterial adversaries with the development of antibiotics.
AstraZeneca uses different vaccine technology to the RNA vaccines from Pfizer and Moderna, but in the future, we may well look back on the first half of the twenty-first century as the time when mankind turned the tables on our viral adversaries with the development of RNA vaccines.
But before RNA vaccines, which we hear a lot about in the battle against Covid, the main ones being developed were ‘whole virus’ vaccines. And some of those were developed in Ireland.
Developing vaccines in response to virus outbreaks, managing clinical trials to prove that novel vaccines work, overcoming technical issues that affect supply, and obtaining regulatory approval are all news items we have become familiar with over the last few months. However, an Irish company was dealing with these issues on an ongoing basis from its establishment in 1992.
The facility – Fort Dodge Laboratories (a division of what was then Wyeth (now Pfizer) manufactured a range of veterinary vaccines, including a canine coronavirus vaccine. The facility provided an innovative environment and represented an exciting time for Irish science, for as well as manufacturing vaccines, the scientists working there were involved in research and development, and in filing applications for regulatory approval of new vaccines.
This Sligo facility was the first to submit a licence application for a genetically engineered vaccine to the then newly established European Medicines Agency in 1995.
The facility is now closed, having succumbed to competition from similar facilities following a corporate acquisition, but for over 24 years it produced millions of vaccine doses annually, targeted at a range of animal diseases and worked to the same exacting quality and regulatory standards as applies to the research and manufacture of human vaccines.
Canine coronavirus vaccines
The canine coronavirus vaccine produced in Sligo was a classic inactivated vaccine. Many human vaccines are also inactivated vaccines, and they consist of dead viral material, which when injected into a patient provokes an immune response so that the patient has immunity if subsequently exposed to the live virus.
However, the development, production and testing of this type of vaccine is extremely time-consuming, as it first involves the culture of the live virus material.
Viruses are parasites, meaning that they need to infect a living cell in order to grow and reproduce. Thus, in order to grow virus material, one must first culture animal cells.
Cells isolated from various organs can be grown in the laboratory using a specialised, sterile liquid that mimics blood and provides the nutrients needed for cell growth.
Following several weeks of culture, several hundred litres of animal cells are produced, and a small amount of virus material is then introduced to the cells. The virus attacks the cells, multiplies inside the cell, bursts out and infects neighbouring cells, and the cycle continues.
After several days, most of the original animal cells are dead, but one now has hundreds of litres of live viral material. Addition of a chemical kills (inactivates) the live viral material, which is then blended with other materials to yield the final, inactivated virus vaccine.
New vaccine technology
Research into RNA vaccines has been conducted for the last three decades and has culminated with the development and approval of the Covid-19 RNA vaccine.
To put the achievement into context, coronaviruses are tiny – millions would fit onto a pinhead. On the surface of this infinitesimally small, invisible particle there is a protein. Scientists have identified the sequence of that protein and used this information to produce the RNA vaccine.
RNA can be produced rapidly in the laboratory and then packaged into lipid particles. When introduced to patients, the RNA is taken up by the patient’s cells, and this RNA then produces the spike protein, which is displayed on the cell surface. Immune cells recognise the spike protein as foreign and manufacture antibodies against it.
Thus, if the patient is subsequently exposed to coronavirus, antibodies will be produced rapidly which will neutralise the virus, and Covid-19 will not develop. The patient has immunity.
With the production of RNA vaccines, there is no large-scale animal cell culture required, which saves a huge amount of time when such vaccines are being developed and manufactured.
RNA-vaccine technology represents a paradigm shift in both the design of vaccines and the speed at which they can be researched, manufactured, tested, and approved. This is one of the reasons why this novel vaccine has been approved in record time.
Also, if a variant viral strain develops, it is a very quick process to produce a modified RNA vaccine targeting the new strain. RNA vaccines also represent a much purer final product and furthermore, once the introduced RNA has done its job, it is broken down inside the cell, so effectively the RNA vaccine delivers its message – the spike protein, and then disappears.
The Future
RNA vaccines are breath-taking in the scientific advancement that they represent, and it is difficult to overstate the potential impact of this scientific breakthrough.
For example, the use of RNA to deliver effective therapies will also be trialled for other conditions ranging from certain types of cancers to cystic fibrosis.
Traditionally the medicines that have been developed by the pharmaceutical industry have been simple chemical compounds that can be manufactured quickly by chemical synthesis. The development of RNA vaccines has highlighted the rapidly growing trend in new drug development which focuses on biological materials such as DNA, RNA, proteins, and antibodies.
These new drugs or ‘biologics’ are more targeted, have fewer side effects and are more powerful than traditional medicines. However, they are often manufactured using living cells, and consequently, they are more difficult to produce, timelines for production and testing can be large, and yields can vary greatly from batch to batch. This explains some of the shortfall in supply that we are experiencing with the various Covid vaccines.
The technology used in RNA vaccines overcomes a lot of the above issues, and the use of biologics also greatly facilitates the development of personalised medicines and now represent the main area of focus for new drug development in many of the larger pharmaceutical companies. The age of biologics has arrived.
Dr Seamus Lennon is Covid Officer and Head of Department of Biopharmaceutical and Medical Science at the Galway Mayo Institute of Technology (GMIT) and previously worked at Fort Dodge Laboratories, Sligo, as Quality Manager.
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