With the news this week that the first vaccine against COVID-19 may be available within weeks I have been asked many questions about it, from “How can it be safe to inject the virus into a person?” to “Will you be having it?”
In this piece I will lay out some of the questions I have been asked so far with answers based on the scientific evidence available.
Background to the Most Promising Vaccines
The vaccine making headlines this week has been developed by the German biotechnology company BioNTech in conjunction with the drug company Pfizer. It is based on a similar principal to the one currently in its final trial stages at Oxford University and manufactured by AstraZeneca in that they both target the protein spikes on the surface of the virus although the technology involved in producing them is different. (1) (2)
These two vaccines, along with one by the US company Moderna, are emerging as the most likely candidates for widespread use. The background to these and other vaccines is covered here in the piece “The Race for a Vaccine.”
During clinical trials, contrary to popular belief, trial participants are not deliberately infected with COVID-19. Although this approach, known as Challenge Trials, is sometimes used in research it is only done so when there is a wealth of pre-existing knowledge about the illness and well established treatments that will successfully treat any subsequent illness. Neither of these two parameters currently apply to COVID-19. It is possible that Challenge Trials may be given the go ahead early next year but they may not be needed if a successful vaccine is already becoming available by then. (3)
Without Challenge Trials it takes months of monitoring for enough people to become exposed to the illness for any results to be reliable. What researchers hope to see is that amongst those who have received the vaccine few, if any, go on to contract the illness whilst those who received a placebo injection continue to catch the illness at the expected rate. If nobody in a trial catches the illness this is not as good as it sounds as it makes it impossible to know if the vaccine achieved anything.
The Pfizer-BioNTech trial enrolled 43,538 participants who were split into two groups. Half received the vaccine, the other half a placebo injection. Participants do not know which they have received. 94 trial participants have gone on to have a confirmed COVID-19 infection so far. Pfizer-BioNTech have not yet said how those cases were split between the vaccine and placebo groups but have announced that the vaccine was 90% effective in preventing infection. This means that for every 10 cases in the placebo group there was just one in the vaccine group. The trial will continue until a total of 164 COVID-19 cases are detected. (4)
Oxford-AstraZeneca are due to release their preliminary data later this month.
Question: How can it be safe to have the vaccine when it gives you the virus we’ve all been trying to avoid?
Answer: Firstly the vaccine does not contain the virus.
Neither the Pfizer-BioNTech vaccine nor the candidate from the Oxford-AstraZeneca team contain the virus itself or an inactivated form of the virus.
Instead these vaccines target the club-shaped spikes seen on the surface of the virus. Researchers have isolated the genetic code, the RNA, of these surface spikes and have been able to attach that code to a known harmless virus in the case of the Oxford-AstraZeneca vaccine and to a liposome (a small fat cell) in the case of the Pfizer-BioNTech vaccine. This forms the basis of the vaccine and once injected into the body the immune system believes it is the genuine coronavirus and mounts an immune response to it.
This is different to the older methods of vaccine manufacture which do use an inactivated version of the virus, known as the antigen, created by weakening and inactivating the virus through chemical processes.
Question: I don’t want a “foreign” genetic code injected into me, isn’t that dangerous?
Answer: These two vaccines do contain mRNA (the m stands for “messenger”), the genetic code from the spikes on the surface of the coronavirus. At first glance, it is understandable that people are worried that having the vaccine means introducing foreign or rogue genetic material into humans.
However, every time we catch a viral illness that virus infects us by introducing its genetic material into our cells. The common cold is caused by a variety of viruses including some from the coronavirus family. Every time you have had a cold that virus has inserted its mRNA into your body’s cells, specifically those of the nose and throat in the case of the common cold. The vaccine is simply replicating what we know happens with every viral illness.
As humans, our genetic code is contained within our DNA, a double stranded molecule in all of our cells that is far more complex than RNA which is a more simple, single strand. RNA and DNA have different chemical contents and structures to each other which means RNA from a virus (or vaccine) cannot integrate itself into our DNA. Also human cells cannot convert the RNA into DNA. DNA is not a double stranded molecule because it’s two strands of RNA twisted together, DNA and RNA are completely separate entities. (5)
These vaccines do not interact with or alter your own DNA. They are seeking to mimic, rather than replicate, the illness in our bodies allowing our immune systems to kick in and do the rest.
Question: This is brand new technology, how can I be sure it is safe?
Answer: Using RNA as part of a therapeutic treatment is not a new idea. Research has been ongoing for the last two decades and there are now several established and fully licensed drugs known as oliginucleotides that use RNA. They are being used as cancer treatments and in some very serious, life-limiting illnesses such as Duchenne Muscular Dystrophy and Batten disease, a fatal neurological disease in children. There does not yet appear to be any sign of significant side effects from their use. (6)
One of the biggest hopes for the future treatment of cancer is that there will be “cancer vaccines” tailored to individual cancers. RNA technology is at the forefront of this research and BioNTech one of the institutes working on it. (7)
The Oxford team working alongside AstraZeneca have previously produced a vaccine for MERS (Middle Eastern Respiratory Syndrome), an illness also caused by a coronavirus and transmitted to humans from camels. The vaccine also uses RNA technology and is now in final phase III trials across Saudi Arabia where most cases of MERS occur. (8) (9) (10)
Question: These vaccines are being rushed through, how can that be safe?
Answer: The most important issue with vaccine research is the quality of the studies, rather than the time taken to carry them out. A vaccine that has been studied for several years in a few hundred people is not necessarily safer than one whose research was carried out in under a year in more than 43,000 people.
I would agree that this vaccine has been "rushed" - although a better word would be “expedited” - it needed to be. The pandemic has devastated countries around the world, killing more than 1.3 million people. In the UK alone more than 50,000 people have now died.
None of the usual steps in vaccine research and production have been missed out. In more normal times research results are not submitted until the very end of any drug or vaccine trial but this time results have been continuously submitted and analysed. Not only does this help speed up the production of potentially successful vaccines but also means that time is not lost researching unpromising candidates. The trials in humans have taken the same amount of time as they always do. It is much of the administration side of vaccine research, such as funding and gaining ethical approval for studies, that has been dealt with far more quickly than normally.
The other thing to consider is that vaccine trials have to be carried out in places where the disease is spreading. This can cause delays and hold up research if the disease being studied fluctuates in its prevalence. Given the relentless onslaught of the COVID-19 pandemic it has been very easy for scientists to run their trials virtually anywhere in the northern hemisphere. (11)
The Pfizer-BioNTech vaccine is not yet available to the public, it is important to remember that the research process has not finished with the announcement this week. We have only had the preliminary news that it appears to be working and to be safe. The data will now be studied and analysed by peer groups outside of the original research scientists before any submission is made requesting authorisation to administer it to the public. (12)
The criticism that this virus has been made too quickly should perhaps be turned on its head and the real question we should be asking is “Why can’t all vaccines be made this fast?”
Question: As a doctor, would you have this vaccine?
Answer: If this vaccine is declared safe and effective after the data has been published and analysed then my answer is “Yes”. This analysis is about to happen with the Pfizer-BioNTech vaccine and the Oxford-AstraZeneca data is not far behind. The processes behind both these vaccines have thus far followed every step of reputable vaccine development and there is no reason to believe this vital final step will be any skipped.
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