A health care worker holds an injection syringe of the phase 3 vaccine trial, developed against the novel coronavirus (Covid-19) pandemic by the U.S. Pfizer and German BioNTech company, at the Ankara University Ibni Sina Hospital in Ankara, Turkey.
Dogukan Keskinkilic / Anadolu Agency via Getty Images
For ten bleak months, the prospect of an effective coronavirus vaccine has been the light at the end of the tunnel. That light is now burning somewhat brighter with the news that a vaccine candidate has shown very promising results during clinical trials. At a UK government press conference on November 9, England’s deputy chief medical officer Jonathan Van-Tam called the vaccine a “scientific breakthrough”.
But how much of a breakthrough is it, exactly? We still don’t know. The vaccine, developed by pharmaceutical giant Pfizer and German firm BioNTech, is still in the middle of its Phase 3 clinical trial and is yet to be approved by regulators. So far, 39,000 people scattered around the world have received two doses of either the vaccine or a placebo and are being carefully observed.
Pfizer has, however, published a press release suggesting the vaccine is more than 90 per cent effective – a move that has left many eager to find out what the full details of the study are to date and when it will be peer-reviewed. We know that this particular vaccine uses a small piece of messenger RNA (mRNA) from the Sars-CoV-2 virus, not the full virus itself, to provoke an immune response. Two doses are required. The trial participants represent a broad range of demographics – 42 per cent are from racially or ethnically diverse backgrounds.
But in any clinical trial, the devil really is in the detail. These are seven key questions to which we need answers before we can be truly confident that life will return to “normal” in the coming months.
Does the vaccine prevent infection or just symptoms?
As Van-Tam, among others, has said, it’s not clear from the information released so far about the trial that the vaccine prevents infection by the Sars-CoV-2 virus or just symptoms of Covid-19. If the vaccine merely stops symptoms developing, it might be possible that someone could take the vaccine and still get Covid-19, though without any noticeable illness. Such an asymptomatic individual might still be able to spread the virus if they shed it in large enough quantities to infect another person.
If – and it remains an “if” – the vaccine does not prevent asymptomatic transmission, its value would be somewhat limited says Eleanor Riley, an immunologist at the University of Edinburgh: “We’re not going to get rid of the virus with a vaccine like that.” It would mean health services would still have to work hard to identify and protect vulnerable people and treat those who end up developing a severe case of Covid-19.
A related question, noted in the British Medical Journal, is whether the vaccine will ultimately have the effect of reducing deaths caused by the disease. The trial itself is not actually designed to measure this and will end once 164 participants test positive for Covid-19, regardless of the severity of their illness. It’s arguable whether this is a serious problem, though, says Riley.
“If you were going to have a trial big enough to pick up a statistically significant difference in deaths, that trial would have to be absolutely enormous and it would have to run for a very long time,” she says. “If it stops people getting sick, it probably stops them getting severely ill.”
What happened to the trial participants who became ill?
Generally, in a clinical trial, participants receive the drug being tested or a placebo. For the Pfizer/BioNTech vaccine, half of the participants received the vaccine but don’t know for sure that they have had it, because the trial is double-blind, meaning they are not told whether they got the vaccine or the placebo.
Pfizer says that 94 people on the trial have so far become infected with Covid-19. And while most of those individuals must have been in the group that received the placebo, given the 90 per cent efficacy figure, we don’t know to what extent the 94 people became ill. Did any develop severe cases of Covid-19, for instance?
Does efficacy depend on the age or health status of the recipient?
One glaring unknown at this point is whether the emergence of Covid-19 is weighted towards older trial participants who received the vaccine, for example. That information should be forthcoming – the study is designed to include people aged 16 and up, with 40 per cent being 55 or older. And what about people with health conditions that make them particularly susceptible to Covid-19, such as heart disease or diabetes?
It’s possible that elderly people, for instance, whose immune systems are generally weaker, might end up requiring different or additional booster shots beyond the first two doses, says Sheena Cruickshank, an immunologist at the University of Manchester.
How long does immunity last?
This one is a biggie. Besides not knowing exactly what sort of immune response the vaccine provokes, we also don’t know how long that response lasts beyond the first week following the second dose of vaccine. The trial will examine what happens next to some extent, over the course of the coming weeks and months, but we won’t know whether immunity lasts for years, for instance, until such time has elapsed.
If it turns out that immunity only persists for six to 12 months, vulnerable people may need to receive the vaccine every year – a bit like with flu vaccines that target whichever strain of flu is spreading that season. “We’d want to vaccinate people every autumn to protect them through the following winter,” says Riley.
Will the vaccine get approval?
In order for the vaccine to actually reach the public, there are multiple hurdles it must yet pass. That includes getting safety approval from regulatory bodies. Approval can come in two stages, with emergency use granted for the rollout of a new drug while an emergency is ongoing and so long as it continues to meet certain standards. A drug can only achieve full approval after significant safety data has accumulated. In the US, the FDA requires a year of data on at least 3,000 trial participants before granting full approval. To date, the Pfizer/BioNTech trial has not reported any serious safety concerns.
While no mRNA vaccine has ever been approved before, Michael Betts, an immunologist at the Penn Institute for Immunology – who has been involved in experiments to test the immune response of a different vaccine candidate – says the early data from trials using mRNA vaccines does not show lots of worrying side effects, meaning that emergency use approval, at least, will likely be straightforward for Pfizer/BioNTech to obtain.
Is it feasible to distribute this vaccine to billions of people?
Some vaccines can be stored at normal fridge temperature and easily transported to wherever they’re needed. But things are trickier with this one. It has to be kept at -70C and in carefully handled containers. According to a presentation slide published online, which has been quoted by Science magazine, the dry ice in the box containing vaccine doses has to be replenished within 24 hours upon delivery, the box can’t be open more than twice in one day and it can only remain open for a maximum of one minute each time.
Not only that, manufacturers will require a vast and reliable source of materials such as glass vials so that they can produce and package billions of doses of the vaccine. Ensuring all of this goes to plan and the vaccine is delivered in appropriate conditions all around the world is not easy. The requirements for keeping it very cold only add to the expense and complexity of the operation. As does the fact that recipients need to get two doses at the right time, three weeks apart.
Pfizer/BioNTech say they plan to have mass produced 50 million doses by the end of 2020 and a further 1.3 billion doses by the end of next year. “I think that where there is a will, there is a way on this one,” says Betts. Authorities will likely design mass vaccination programmes that use large freezers to store the vaccine in, he adds.
What are the UK’s plans for getting people vaccinated?
The health secretary Matt Hancock has, somewhat cryptically, asserted it is “absolutely a possibility” that the first doses of the vaccine could reach Brits by Christmas. The UK has already ordered enough to vaccinate 20 million people, roughly a third of the population.
The Joint Committee on Vaccination and Immunisation currently intends to distribute the vaccine to care home residents and workers first, then people aged 80 or over and all health and social care workers. After that, people aged 75 and over will receive it, then 70 and over and so on until – perhaps – a scheme for vaccinating the wider population is in place. But this schedule could change should new information come to light suggesting, for instance, that the vaccine is less effective in older people.
Nobody knows whether any logistical disruptions caused by Brexit could affect the rollout of the vaccine. Nor how quickly the UK will get its hands on the millions of doses it has ordered, or any additional doses beyond that first batch.
Given this, and the remaining uncertainties about exactly how well the vaccine is performing for all participants in the trial, it’s important to continue social distancing, wearing masks and washing our hands in order to protect one another for some time, says Riley. “That is not going to change for the vast majority of us this winter – we’ve got to stick with what we’re doing or a minor variation of it into the spring,” she says.
But, it’s fair to say, with news of the vaccine comes a much-needed glimmer of hope. “We could be in a much better position by the summer,” says Riley.
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