- Pfizer, BioNTech and Moderna have pioneered a new method for developing vaccines which has led to rapid production of a Covid-19 vaccine
- Questions are being asked of the regulatory and roll-out process
Unprecedented. There is no doubt that the word has been overused in 2020 – a savage virus, restrictive governments and national lockdowns are rare and exceptional, but not, as Oxford’s dictionary defines unprecedented, ‘never known before’.
Vaccine development is different. There is no precedent for the pace at which coronavirus vaccines have been created in 2020. And – in the case of the Pfizer/BioNTech and Moderna vaccines – there is no precedent for the modus operandi either. Released into a world increasingly nervous about vaccination by regulators that are at the mercy of desperate governments could seem ominous.
But Pfizer (US:PFE) and Moderna’s (US:MRNA) rapid vaccine development should not be too surprising given recent progress in genetic engineering.
On 10 January 2020, Chinese scientists published the genome for the SARS-CoV-2 virus, which had infected a handful of citizens who had entered a live animal market in Wuhan and caused the illness we now know as Covid-19. The virus had a similar genetic make-up to the strain of coronavirus that caused the 2003 SARS outbreak, but a few striking differences meant that scientists quickly recognised that no-one would be immune to the illness. By the time it had become clear that SARS-CoV-2 could leap from person to person with alarming efficiency, pharma companies and researchers around the world had begun to work on a vaccine.
Genetics to the rescue
Vaccines can provide effective protection against viruses because of the way they infect cells and cause illness. Unlike animals, plants, or even bacteria, viruses are neither living nor dead; instead they insert snippets of genetic code into a living cell where it is transcribed into messenger RNA (mRNA). This mRNA wreaks havoc by building virus proteins, which become part of their hosts’ cells. Fortunately, living organisms have a mechanism for dealing with such attacks – after identifying the virus, the immune system sends antibodies to suffocate and kill the virus proteins.
It is that process which German scientists Uğur Şahin and Özlem Türeci sought to utilise when they set up their vaccine company, BioNTech in 2008. They theorised that injecting specific messengers which code for a virus's identifiable protein (known as the spike protein) will alert the host’s immune system to the virus, without actually causing an illness. The theory worked in the lab and, by 2018, the company had captured the attention of pharma giant Pfizer, which entered into a multiyear research and development collaboration to develop mRNA-based vaccines for the prevention of flu.
Enter SARS-Cov-2 and the genome carefully mapped out by Chinese scientists, identifying the code for the virus’s spike protein. Experts at BioNTech’s site in Germany were able to create a synthetic version of the genetic code and quickly turn it into a usable vaccine, which entered clinical trials in March. In November, the company became the first to announce positive results from its large-scale study: the vaccine prevents the development of symptomatic coronavirus in 95 per cent of cases.
Since then, Moderna’s vaccine – which also uses the mRNA mechanism – has reported similarly successful raw data, while Oxford University’s more traditional vaccine, which uses an inactivated form of the virus, wrapped up in a common adenovirus, has achieved clinical success in a smaller population.
Regulation: rapid turnaround?
All three vaccines are now being assessed by international regulators, with the UK’s Medicines and Healthcare Regulatory Agency (MHRA) expected to pass judgement on the Pfizer vaccine within days. According to foreign secretary Dominic Raab, the government wants “to be in a position to be able to have rolled out the vaccine sufficiently by the spring to enable us to have a big change in the way we approach things”.
But regulators should beware the influence of commercial and political pressure. In the UK, the government is in desperate need of an escape route from lockdown; Boris Johnson and his team cannot release the country from tight restrictions without admitting that lockdown might have been the wrong course of action, nor can they continue to shut up society without facing severe economic destruction. A vaccine will allow the UK government to claim that it is now safe to release restrictions.
Meanwhile, pharma companies want to begin making money from their research. Raw data from tiny populations is being released to the public far earlier than it would be in vaccine trials in ordinary times. But, as Professor Peter Doshi argues in the British Medical Journal, “let’s be cautious and first see the full data”. Pfizer, Moderna and AstraZeneca (AZN) have all reported success in the small fraction of study participants who have caught coronavirus – 170 participants for Pfizer, 95 at Moderna and 131 for AstraZeneca. These participants have only been tested soon after vaccination, meaning there is no data on long or even mid-term immunity. Meanwhile, certain population sub-groups, including those most vulnerable to coronavirus, have not been tested at all. Questions are also being asked of the testing methodology, which sought to examine symptomatic Covid-19 rather than the underlying presence of the illness.
“I previously argued that the trials are studying the wrong end point,” says Professor Doshi, “it’s hard to avoid the impression that sponsors are claiming victory and wrapping up their trials.”
Curb your enthusiasm
And even if the vaccines are as good as they appear from initial data, optimism should be kept in check. Vaccine deployment that is sufficient to stifle the virus and allow the UK to get back to normal by the Spring is far easier said than done. China and Russia might have managed to roll out questionably-tested vaccines to huge swathes of their populations, but mass vaccination efforts have never had much success in democratic societies. In the UK, the government is unlikely to enforce vaccination – it is already fighting too many comparisons with oppressive, tyrannical states.
Looking ahead to 2021, the NHS is facing an excruciating backlog of ‘elective’ operations and is therefore likely to struggle to coordinate a national roll-out of a novel vaccine that requires two doses, especially at a time when those who need it the most are being advised to stay away from hospitals, queues, or anywhere that they might pick up Covid-19.
Medical centres will also have to battle the Pfizer/BioNTech vaccine’s unfortunate storage challenge: the lipid-casing of the vaccine, which allows the mRNA code to safely enter the target cell, disintegrates in normal temperatures, meaning the vaccine must be stored at -70 degrees. Not many hospitals have large enough storage facilities for huge volumes of deeply frozen vaccine. Pfizer has developed its own packaging to keep doses cold, but that only gives 10 days of storage before the need for specialised freezers.
The good news is that manufacturing of the vaccine itself shouldn’t be a problem. mRNA vaccines aren’t that difficult to produce in large quantities because they don’t require live cells. Traditional vaccines are grown in living organisms (historically chickens eggs) in a process that can take several months, but mRNA vaccines use synthetic code which can be whipped up by scientists quickly – as long as they know what the genome of the spike protein is. This has the added benefit of making mRNA vaccines easy to alter if the virus mutates.
What’s more, mRNA vaccines are highly potent, which means only a small sample of active ingredient is needed for a large batch. The Pfizer/BioNTech vaccine is especially efficient and requires just 30 micrograms of mRNA per dose, compared with 100 micrograms for the Moderna vaccine. This means that large volumes of the shot can be made with relatively little effort.
Pfizer has plants in the US and Belgium which have already begun large-scale production, and the company thinks it can produce 1.3bn shots in 2021. But supply of those vaccines might be an issue. Both of Pfizer’s manufacturers are at the mercy of global supply chains, which have been hugely disrupted by lockdown. Many pharmaceutical manufacturers rely on the hold compartments of commercial airlines for transport of goods and so travel restrictions and the grounding of aeroplanes means capacity is currently very low.
All that we need
So, while proclamations of an end to the pandemic by Spring 2021 might be optimistic, there is a light at the end of the tunnel. To return to normality, the UK doesn’t need to vaccinate everyone; it only needs to inoculate those at highest risk from severe Covid-19 symptoms – the frail and the elderly. If these people can be protected, the wider population can begin to build immunity through constant exposure to the virus.
Indeed, scientists are increasingly optimistic that a degree of so-called herd immunity has been achieved in areas where the virus first landed in the UK – London, for example, has had a far less severe ‘second wave’ than towns and cities which were locked down before the virus had a chance to spread.
As for the vaccine, effective or not, readily available or in short supply; its development has been a lesson in remarkable international co-operation and scientific progress. The process by which Covid-19 vaccines have been developed can now be utilised in other illnesses for which vaccination was previously impossible – HIV and cancer, for example. Perhaps, the world would still be waiting for its first genetically developed vaccine if it wasn’t for the global pandemic. If coronavirus has a silver lining, that is it.