The race for a COVID vaccine has four candidates nearing the finish line — with some getting ready to roll out before the end of the year. But what do the reported efficacy results actually mean and how much will doses cost? We break it down.
In the fast-paced world of COVID vaccines, November was a particularly busy month. The early data of four jabs was announced — with most of the jabs showing efficacy of 90% or higher. And one of them has already been granted approval for emergency use in the United Kingdom (UK), the United States, Canada and Mexico.
A 90% efficacy means that nine in ten people who received the shot in trials — as opposed to a placebo or dummy vaccine — did not develop COVID symptoms or were protected from the disease, COVID-19.
Vaccines are the most powerful tool we’ve got to fight COVID-19 and our biggest hope for at least some normality to return to our lives.
But the data we have so far is not final information. These results were first shared via press releases — not peer-reviewed scientific journals, as is the norm. On Tuesday, The Lancet was the first to publish data from a COVID vaccine for the AstraZeneca and Oxford University candidate. This was then followed by the publication of results for Pfizer and BioNTech’s candidate in the New England Journal of Medicine on 10 December. Although the urgent need for a COVID vaccine has necessitated the release of the data as it becomes available, it’s important to remember that the figures can still change as they go through more checks and balances.
There are also questions that we can’t yet answer — such as how long the immunity provided by any of the four frontrunner vaccines can protect people — without long-term monitoring of people who receive the shots. There is also more about the studies that we will only learn once the final results have been shared in a publication, such as additional detail on what each study was measuring — for instance, if a jab influenced how severe COVID cases were. Once these finer points have been shared, in the form of a scientific paper, it wil be easier to assess the efficacy of the vaccines as it will be clearer what is being compared.
Efficacy refers to how well a vaccine works in a controlled, trial setting. The effectiveness of a jab, on the other hand, is something different. That tells us how well a vaccine performs in the real world, where things like the level of training of healthcare workers who give the shots or the quality of cold-chain systems can interfere with the vaccine’s outcomes.
So, efficacy does not necessarily translate to effectiveness in real life.
It is only once a jab has been rolled out on a large scale that we would begin to see how it performs outside these ideal clinical conditions.
While countries like the United States and UK are speeding ahead with approval, this will not be South Africa’s plan of action, says Barry Schoub, chair of South Africa’s ministerial advisory committee on coronavirus vaccines. In large part it is because South Africa does not have the expendable income to buy massive amounts of multiple vaccine candidates and will instead be taking a more considered approach to selecting which jabs should be procured, he says.
“We have to think very, very carefully about what vaccine to recommend and what to go for. At this point we still need to know a lot more about the vaccines before we think about procuring one,” cautions Schoub.
So with all that in mind, what do these results actually mean?
We’ve broken it down to help you keep track of the COVID vaccine frontrunners.
1. Pfizer/BioNTech
What were the results?
Pfizer/BioNTech were the first companies to announce their vaccine results. The manufacturer reported 95% efficacy in its mRNA-based jab, when measured from 28 days after participants received the first injection. But it’s likely the vaccine would start to offer some protection and begin to stimulate an immune response from as early as 10 days after receiving the first dose, says Schoub. The initial data shows the vaccine was able to offer protection to trial participants regardless of whether or not they had previously been infected with SARS-CoV-2, the virus that causes COVID-19. Efficacy was slightly lower — 94% — in people over the age of 65.
How many COVID-19 cases were analysed?
All studies have specific “endpoints” that they’re looking to measure. In this case, one of the main outcomes was to see how many people in the vaccinated trial group got COVID-19 and to then compare that to the COVID-19 cases in the control group that were injected with a dummy vaccine.
This analysis took place once 170 cases had been reported — representing roughly 0.4% of the people enrolled in the study. Of these, 162 infections were in people who received a placebo and eight were among those who were injected with a vaccine.
How soon will the shot be available?
Pfizer and BioNTech received authorisation to market and distribute their vaccine in the UK on 2 December. The temporary approval for emergency use, which comes from the country’s regulatory body, means the UK is set to begin rolling out the first of its 40-million doses on Tuesday, according to a statement from the country’s National Health Service. The UK government has said that it will initially prioritise elderly people in long-term care homes and healthcare workers, in line with recommendations its independent Joint Committee for Vaccination and Immunisation.
Pfizer and BioNTech have also applied for emergency use authorisation with the United States’ medicine regulator, the Food and Drug Administration (FDA). This was granted on 11 December and allows the companies to market and distribute their vaccine among high-risk populations such as health workers. As soon as the approval was granted, Pfizer began shipping doses immediately. Millions of doses are expected to be delivered across America this week, according to Gus Perna, the CEO of Operation Warp Speed, which aims to fast-track the development of COVID vaccines in the US. Moreover, the companies have begun seeking regulatory approval for their candidate in other countries, including: Australia, Canada, Europe and Japan.
What will it cost?
The US government paid $1.95-billion for the first 100-million doses of the vaccine, averaging out to roughly $20 per dose (approximately R305).
Although, according to Schoub, South Africa is not looking to secure this vaccine directly from Pfizer/BioNTech, the country has submitted a non-binding confirmation of intent to participate in COVAX and will be making its first payment by 15 December. COVAX is an initiative run by the vaccine alliance, GAVI, that aims to ensure equitable access to a COVID vaccine when it becomes available. This agreement allows for some lower- and middle-income countries to secure doses for as little as $2, or R30, per dose. But South Africa, which is a higher middle-income country, does not qualify for these reduced or subsidised rates.
What would rolling out the vaccine involve?
This is a two-dose vaccine, with the second injection given at 3 weeks after the first. This means that everyone who receives the jab will need to return for the next shot, which poses a potential logistical challenge in terms of follow-up. South Africa’s current immunisation programme, which focuses on children, would have to devise a new strategy aimed at adults and create a system to ensure people return for both doses.
Another challenge with the jab is that it needs to be kept at well below freezing temperatures, otherwise it could get damaged and become less effective. The vaccine needs to be stored and transported at minus 70 degrees Celsius — a feat for which South Africa is ill-equipped. Although Pfizer says they’ve designed special shipping containers to help maintain this temperature, the shot still requires specialised freezers which are not readily available in South Africa’s healthcare facilities. These unfeasible storage requirements, along with the vaccine’s high price point, means it is unlikely that the jab will be South Africa’s first choice, says Schoub.
2. Moderna/National Institute of Allergy and Infectious Diseases (NIAID)
What were the results?
Moderna reported 94.1% efficacy in its mRNA-based candidate, just slightly less than Pfizer/BioNTech’s jab. The analysis looked at how much protection the vaccine could offer from two weeks after participants received the second injection. Data released by the biotechnology company also shows promise that the jab could prevent people from developing more serious COVID-19 symptoms — all the trial participants who developed severe cases were in the group that received the placebo shot. According to the company’s analysis of the results, it does not look like age, race or gender made any difference to the efficacy of the vaccine.
How many COVID-19 cases were analysed?
The study found 94.1% efficacy based on the analysis of 196 COVID-19 cases observed among participants. This represents roughly 0.7% of all those enrolled in the trial. A total of 185 cases were among those who did not receive the real vaccine and 11 were in those who had been immunised with the actual shot.
Of the reported COVID-19 cases, 30 people had severe symptoms, all of whom were in the placebo group. Additionally, one death was reported in a participant who had not received the vaccine.
How soon will the shot be available?
Moderna submitted applications for emergency use authorisation with the FDA at the end of November. The company is in the process of applying for similar approvals in Europe, Canada, Switzerland, the United Kingdom, Israel and Singapore. Moderna is also applying for emergency use listing with the World Health Organisation. Distribution of doses in the US could begin by the end of the year, pending approval.
What will it cost?
The US government paid $1.525-billion for the first 100-million doses of the vaccine, averaging out to roughly $15 per dose (approximately R229). In October, the company said that it was still in discussions with COVAX regarding tiered pricing for the jab.
Moderna’s CEO Stéphane Bancel told Science the company would charge developed countries between $32 to $37 per dose (R488 to R565), but offer the vaccine at a lower cost to developing countries.
What would rolling out the vaccine involve?
As with Pfizer/BioNTech, this is also a two-dose regimen, with participants receiving the second shot after 29 days. This poses the same follow-up challenges as the Pfizer/BioNTech jab, as health workers would need to find ways to ensure people return for their second shot.
Although nowhere near the requirements of Pfizer/BioNTech’s candidate, this jab needs to be kept at minus 20 degrees Celsius during transportation and for long-term storage. For short-term storage, up to 30 days, the doses can be kept between two and eight degrees Celsius — the temperature of a standard refrigerator. But transportation requirements make it unlikely that South Africa will look to procure this vaccine.
3. AstraZeneca/Oxford
What were the results?
The preliminary data from AstraZeneca/Oxford University’s candidate showed 62% efficacy when people received two full doses one month apart. The study was originally designed to only look at the efficacy of this dosage regimen.
But an error — which was not initially disclosed by either party — resulted in some participants being given different dosages, where they first received a half dose then a full dose a month later.
While participants were never meant to receive this lower dose shot, the research team decided to continue the rest of the trial as planned after discovering the mistake, Mene Pangalos, head of AstraZeneca’s non-oncology research and development, told Reuters.
In a later interview with the New York Times, Pangalos said that no participants were in danger and the dosing change was not disclosed because: “It actually doesn’t matter whether it was done on purpose or not.”
The same article from the New York Times refers to a statement from AstraZeneca’s spokesperson, which had been attributed to Oxford University, that says the error was due to a manufacturing error and had since been fixed.
The dosage regimen where participants received half a dose followed by a full dose one month later, showed 90% efficacy. Combining the results of the two different dosage regimens allows the analysis to reach an average efficacy of 70%.
One possible reason for this higher protection rate is that the group which received the erroneous half dose was roughly a third of the size of those that received the two full doses and have likely been followed up for a shorter period of time, meaning they may not have developed any COVID-19 symptoms yet.
Another limitation on the data is that participants who received the half dose were all under the age of 55 and less likely to develop severe COVID, according to Moncef Slaoui, head of Operation Warp Speed, which aims to fast-track the development of COVID vaccines in the US. Slaoui was speaking on a call with reporters on 24 November.
The pharmaceutical company’s CEO, Pascal Soriot, told Bloomberg News that it would be pursuing an additional global study to confirm the results seen in people who first received a half dose of the jab followed by a full dose.
How many COVID-19 cases were analysed?
A full analysis of the data has yet to be released for the vaccine. The current efficacy reported is based on 131 COVID-19 cases among participants. But details on how these cases were split between the placebo group and those who got the actual vaccines, as well as between the two dosing regimens, were not initially made public. AstraZeneca’s statement also said the data from three different trials — in the UK, Brazil, and South Africa — were being combined in the analysis.
The analysis published in The Lancet on Tuesday showed that there were 27 COVID-19 cases in the group that received the two full doses as opposed to 71 cases in those who received the placebo, or dummy, shot. In the other dosing regimen, where people first received a half dose of the vaccine, the 90% efficacy finding was based on 33 cases — 30 of which were among those who did not receive the real vaccine.
How soon will the shot be available?
Despite the questions raised by the early information shared on the jab, AstraZeneca has announced it has begun seeking regulatory approval for its candidate. Although the exact countries the company is submitting applications to has not yet been disclosed, it is likely that the vaccine will receive approval in the United Kingdom or from the European Union first. In addition, AstraZeneca will also be applying for an emergency use listing from the World Health Organisation and would require FDA approval to market its vaccine in the United States.
What will it cost?
AstraZeneca and Oxford University’s vaccine is the cheapest of the options, available for a tenth of the cost when compared to Moderna’s jab. The pharmaceutical company has already committed to being part of the COVAX agreement at between $2 and $3 (approximately R30 to R45) per dose.
In June, AstraZeneca reached an agreement with Gavi and its COVAX partner, the Coalition for Epidemic Preparedness Innovations (CEPI), to provide 300-million doses starting at the end of the year for $750-million, plus an additional one billion doses for low- and middle-income countries.
What would rolling out the vaccine involve?
Like the other leading COVID jabs, this vaccine involves two doses which are given a month apart. In comparison to the mRNA-based vaccines, this is a longer gap between injections, but it presents the same logistical challenges to follow-up with those immunised.
Unlike its mRNA counterparts, this viral vector jab can be stored at temperatures between two and eight degrees Celsius. Given that this is the standard temperature at which most vaccines in South Africa’s childhood immunisation programme are kept, and does not require any specialised cooling equipment, the AstraZeneca/Oxford candidate is — so far — the most accessible to developing countries.
As one of the trial sites currently testing the vaccine, there is a higher likelihood that South Africa will be able to secure doses in recognition of its contributions to the study’s results — but South Africa is not necessarily guaranteed access to the shot. The country’s involvement in the trial also means there will be data showing the safety and protection the jab can offer in its population.
4. Gamaleya Centre for Epidemiology and Microbiology
What were the results?
In late November, Russia’s Sputnik V candidate, developed by the Gamaleya Centre for Epidemiology and Microbiology in Moscow, reported 91.4% efficacy in participants 28 days after receiving the first dose. Preliminary data shows that the efficacy could increase to over 95% at 42 days after participants are first inoculated.
This new interim data follows skepticism from researchers in the field as to the validity and significance of the numbers because of the small sample group on which the figures were based.
How many COVID cases were analysed?
Although the efficacy reported is on par with its peers, the sample group for this analysis is much smaller. The analysis includes 39 confirmed COVID-19 cases among the 40 000 participants of the trial. Of these, 31 occurred in people who had received the placebo shot and 8 were among those who had been vaccinated.
Another interim analysis will be released once 78 COVID cases have been observed amongst participants.
How soon will the shot be available?
The jab gained notoriety as the first registered COVID vaccine in Russia, before phase three clinical trials had concluded. This phase is usually considered the final stage in a series of tests before seeking regulatory approval if the vaccine turns out to be effective.
Preliminary approval documents have been submitted to Brazil’s regulatory body along with an application for emergency use listing from the World Health Organisation.
The Russian Direct Investment Fund (RDIF) is looking to have doses ready for rollout by March next year.
What will it cost?
Although the exact cost is still unknown, Russia’s sovereign wealth fund, RDIF, has committed to providing doses for less than $10 each.
What would rolling out the vaccine involve?
Like the other frontrunners, the jab is given in two doses, with the second shot given three weeks after the first one. The vaccine will therefore require follow-up to ensure people return for the next injection.
This jab relies on the same technology as the Astrazeneca/Oxford vaccine. Its use of an adenovirus viral vector design makes it more stable at lower temperatures, as such vaccines do not require any specialised storage equipment.
[Updated 11:30 9 December 2020: This article was updated to reflect data from the AstraZeneca/Oxford University COVID vaccine that was published in The Lancet on Tuesday.]
[Updated 10:30 14 December 2020: This article was updated to reflect new emergency use authorisations granted to the Pfizer/BioNTech candidate and that results from the study had been published in the New England Journal of Medicine.]
