Ina
The Living Force
The vaccine outlook in South Africa. I am reproducing the entire article below as it is a good summary of the spectrum of vaccines in question. It is representative for mainstream thinking, but it is pragmatic and comprehensive. As I mentioned elswhere, we, here, are just shy of ‘window shopping’.
A vaccine is our most powerful tool in the fight against Covid-19 and our biggest hope for at least some normality.
But the data we have so far are not final. These results were shared in press releases, not in peer-reviewed scientific journals. Although the urgent need for a Covid-19 vaccine has necessitated the release of the data as they become available, the figures can change as they go through more checks and balances.
There are also questions that we can’t answer yet, such as how long the immunity provided by any of the four frontrunner vaccines can protect people, without monitoring them in the long term. There is also more about the studies that we will only learn once the final results have been shared in a scientific paper, including detail on what each study was measuring, such as whether a jab influenced how severe Covid-19 cases were. Once these finer points have been shared, it will be easier to assess efficacy.
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.
With all that in mind, what do these results mean?
We’ve broken it down to help you keep track of the vaccine frontrunners.
Pfizer/BioNTech
What were the results?
Pfizer and BioNTech were the first to announce their vaccine results. They reported95% efficacy in their mRNA-based jab, when measured from 28 days after participants received the first injection. But it would probably start to offer some protection and begin to stimulate an immune response from as early as 10 days after the first dose, says Schoub. Efficacy was slightly lower (94%) in people over the age of 65.
How many Covid-19 cases were analysed?
All studies have specific “endpoints” to measure. In this case, one of them was to see how many people in the vaccinated trial group got Covid-19 and compare that with the Covid-19 cases in the control group who received a dummy vaccine.
This analysis was done once 170 cases had been reported, representing roughly 0.4% of the people in the study. Of these, 162 infections were in people who received a placebo and eight were among those who were injected with the vaccine.
How soon will it 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 US’s medicine regulator, the Food and Drug Administration (FDA). If their application is successful, they will be allowed to market and distribute their vaccine among high-risk populations such as health workers. According to the director of the US’s National Institute of Allergy and Infectious Diseases, Anthony Fauci, the vaccine will probably be rolled out before the end of 2020 if the application is approved. The companies have also begun seeking regulatory approval 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 (about R305).
Schoub says that while 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 2020.
COVAX is an initiative run by the vaccine alliance GAVI, which aims to ensure equitable access to a vaccine when it is available. This agreement allows for some lower- and middle-income countries to secure doses for as little as $2, or R30. South Africa, a higher-income country, does not qualify for these rates.
What would the rollout involve?
This is a two-dose vaccine, with the second given at three weeks after the first, which poses a potential logistical challenge. South Africa’s immunisation programme, which focuses on children, would have to devise a strategy aimed at adults and create a system to ensure people return for the second dose.
Another challenge is that the vaccine needs to be kept at below freezing temperatures, or it could be damaged and become less effective. It must be stored and transported at -70C, a feat for which South Africa is ill-equipped. Although Pfizer says it has designed special shipping containers to help maintain this temperature, the shot still requires specialised freezers, which are not readily available in South African healthcare facilities. These unfeasible requirements and the high price mean the jab will probably not be South Africa’s first choice, says Schoub.
Moderna/National Institute of Allergy and Infectious Diseases
What were the results?
Moderna reported 94.1% efficacy in its mRNA-based candidate, just slightly less than Pfizer/BioNTech’s. The analysis looked at how much protection the vaccine could offer from two weeks after the second shot. Data also show the jab couldprevent people from developing more serious Covid-19 symptoms. All the participants who developed severe cases were in the placebo group. According to the company’s analysis, it does not look like age, race or gender made any difference to the vaccine’s efficacy.
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 those in the trial. A total of 185 cases were among those who did not receive the real vaccine and 11 were in those who did.
Of the reported cases, 30 people, all in the placebo group, had severe symptoms. One death was reported. The participant 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. It is applying for similar approvals in Europe, Canada, Switzerland, the UK, Israel and Singapore. It is also applying for emergency-use listing with the World Health Organisation. Distribution of doses in the US could begin by the end of 2020, pending approval.
What will it cost?
The US government paid $1.525-billion for the first 100 million doses of the vaccine – an average of $15 per dose (about R229). In October, the company said it was still in discussions with COVAX regarding tiered pricing for the jab.
Moderna CEO Stéphane Bancel told Science the company would charge developed countries between $32 and $37 per dose (R488 and R565), but offer the vaccine at a lower cost to developing countries.
What would rolling out the vaccine involve?
This is also a two-dose regimen, with the second shot given after 29 days. This poses the same follow-up challenges as the Pfizer/BioNTech jab.
Although nowhere near the requirements of Pfizer/BioNTech’s candidate, this jab needs to be kept at -20C during transport and for long-term storage. For up to 30 days the doses can be kept between 2 degree Celsius and 8 degree Celsius, the temperature of a standard fridge. South Africa will probably not buy this vaccine owing to the transport requirements.
AstraZeneca/Oxford University
What were the results?
The preliminary data 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 regimen.
But an error – which was not initially disclosed by either party – resulted in some participants being given different dosages – a half-dose and a full dose a month later.
While they were never meant to receive the lower dose, the research team decided to continue the trial after discovering the mistake, Mene Pangalos, head of AstraZeneca’s non-oncology research and development, told Reuters.
Pangalos told the New York Times 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 refers to a statement from AstraZeneca’s spokesperson, which had been attributed to Oxford University, that says the mistake was due to a manufacturing error and had since been fixed.
The regimen showed 90% efficacy. Combining the results of the two different doses gives an average efficacy of 70%.
One possible reason for this higher protection rate is that the group that received the half-dose was roughly a third of the size of the other and had probably been followed up for a shorter period, meaning they may not have developed any Covid-19 symptoms yet.
Another limitation on the data is that those who received the half-dose were all under 55 and less likely to develop severe Covid-19, 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 24 November.
The company’s CEO, Pascal Soriot, told Bloomberg News it would be pursuing an additional global study to confirm the results seen in people who first received a half-dose.
How many Covid-19 cases were analysed?
A full analysis of the data has yet to be released. 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 vaccine, as well as between the two dosing regimens, have not yet been made public.
AstraZeneca’s statement also said the data from two different trials – in the UK and Brazil – were being combined in the analysis.
How soon will the shot be available?
AstraZeneca has announced it has begun seeking regulatory approval for its candidate. Although the countries to which it is submitting applications have not been disclosed, the vaccine will probably be approved by the UK or the European Union first. AstraZeneca will also apply for an emergency-use listing from the WHOand would require FDA approval to market its vaccine in the US.
What will it cost?
AstraZeneca and Oxford’s vaccine is the cheapest – a tenth of the cost of Moderna’s jab. The firm has already committed to being part of the COVAX agreement at between $2 and $3 (R30 and R45) per dose.
In June, AstraZeneca reached an agreement with GAVI and its COVAX partner, the Coalition for Epidemic Preparedness Innovations, to provide 300 million doses starting at the end of 2020 for $750-million, and 1 billion doses for low- and middle-income countries.
What would the rollout involve?
Like the other leading jabs, this vaccine involves two doses a month apart. This is a longer gap but presents the same logistical follow-up challenges.
Unlike its mRNA counterparts, this viral vector jab can be stored at between 2 degree Celsius and 8 degree Celsius. Given that this is the standard temperature at which most vaccines in South Africa’s childhood immunisation programme are kept, and that it does not need specialised cooling equipment, the AstraZeneca/Oxford candidate is the most accessible to developing countries so far.
As one of the trial sites, there is a higher likelihood that South Africa will be able to secure doses in recognition of its contributions to the results, but access to the shot is not necessarily guaranteed. The country’s involvement also means there will be data showing the safety and protection the jab can offer its population.
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 the first dose. Preliminary data show the efficacy could increase to more than 95% at 42 days after participants are first injected.
The data follow scepticism from researchers in the field about the validity and significance of the numbers because of the small sample group on which they were based.
How many cases were analysed?
Although the efficacy reported is on par with its peers, the sample group here is much smaller. The analysis includes 39 confirmed Covid-19 cases among the 40,000 participants. Of these, 31 had received the placebo and eight had been vaccinated.
Another interim analysis will be released once 78 Covid-19 cases have been observed.
How soon will it 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 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 from the WHO.
The Russian Direct Investment Fund (RDIF) is looking to have doses ready forrollout by March 2021.
What will it cost?
Although the cost is still unknown, the RDIF has committed to providing doses forless than $10 each.
What would rollout involve?
The jab is given in two doses, with the second given three weeks later.
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, eliminating the need for specialised storage equipment. DM/MC
This story was produced by the Bhekisisa Centre for Health Journalism.
The race for a Covid-19 vaccine has four candidates close to a winning jab, with some getting ready to roll out before the end of 2020. But what do the reported efficacy results mean and how much will doses cost?
A vaccine is our most powerful tool in the fight against Covid-19 and our biggest hope for at least some normality.
But the data we have so far are not final. These results were shared in press releases, not in peer-reviewed scientific journals. Although the urgent need for a Covid-19 vaccine has necessitated the release of the data as they become available, the figures can change as they go through more checks and balances.
There are also questions that we can’t answer yet, such as how long the immunity provided by any of the four frontrunner vaccines can protect people, without monitoring them in the long term. There is also more about the studies that we will only learn once the final results have been shared in a scientific paper, including detail on what each study was measuring, such as whether a jab influenced how severe Covid-19 cases were. Once these finer points have been shared, it will be easier to assess efficacy.
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.
With all that in mind, what do these results mean?
We’ve broken it down to help you keep track of the vaccine frontrunners.
Pfizer/BioNTech
What were the results?
Pfizer and BioNTech were the first to announce their vaccine results. They reported95% efficacy in their mRNA-based jab, when measured from 28 days after participants received the first injection. But it would probably start to offer some protection and begin to stimulate an immune response from as early as 10 days after the first dose, says Schoub. Efficacy was slightly lower (94%) in people over the age of 65.
How many Covid-19 cases were analysed?
All studies have specific “endpoints” to measure. In this case, one of them was to see how many people in the vaccinated trial group got Covid-19 and compare that with the Covid-19 cases in the control group who received a dummy vaccine.
This analysis was done once 170 cases had been reported, representing roughly 0.4% of the people in the study. Of these, 162 infections were in people who received a placebo and eight were among those who were injected with the vaccine.
How soon will it 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 US’s medicine regulator, the Food and Drug Administration (FDA). If their application is successful, they will be allowed to market and distribute their vaccine among high-risk populations such as health workers. According to the director of the US’s National Institute of Allergy and Infectious Diseases, Anthony Fauci, the vaccine will probably be rolled out before the end of 2020 if the application is approved. The companies have also begun seeking regulatory approval 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 (about R305).
Schoub says that while 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 2020.
COVAX is an initiative run by the vaccine alliance GAVI, which aims to ensure equitable access to a vaccine when it is available. This agreement allows for some lower- and middle-income countries to secure doses for as little as $2, or R30. South Africa, a higher-income country, does not qualify for these rates.
What would the rollout involve?
This is a two-dose vaccine, with the second given at three weeks after the first, which poses a potential logistical challenge. South Africa’s immunisation programme, which focuses on children, would have to devise a strategy aimed at adults and create a system to ensure people return for the second dose.
Another challenge is that the vaccine needs to be kept at below freezing temperatures, or it could be damaged and become less effective. It must be stored and transported at -70C, a feat for which South Africa is ill-equipped. Although Pfizer says it has designed special shipping containers to help maintain this temperature, the shot still requires specialised freezers, which are not readily available in South African healthcare facilities. These unfeasible requirements and the high price mean the jab will probably not be South Africa’s first choice, says Schoub.
Moderna/National Institute of Allergy and Infectious Diseases
What were the results?
Moderna reported 94.1% efficacy in its mRNA-based candidate, just slightly less than Pfizer/BioNTech’s. The analysis looked at how much protection the vaccine could offer from two weeks after the second shot. Data also show the jab couldprevent people from developing more serious Covid-19 symptoms. All the participants who developed severe cases were in the placebo group. According to the company’s analysis, it does not look like age, race or gender made any difference to the vaccine’s efficacy.
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 those in the trial. A total of 185 cases were among those who did not receive the real vaccine and 11 were in those who did.
Of the reported cases, 30 people, all in the placebo group, had severe symptoms. One death was reported. The participant 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. It is applying for similar approvals in Europe, Canada, Switzerland, the UK, Israel and Singapore. It is also applying for emergency-use listing with the World Health Organisation. Distribution of doses in the US could begin by the end of 2020, pending approval.
What will it cost?
The US government paid $1.525-billion for the first 100 million doses of the vaccine – an average of $15 per dose (about R229). In October, the company said it was still in discussions with COVAX regarding tiered pricing for the jab.
Moderna CEO Stéphane Bancel told Science the company would charge developed countries between $32 and $37 per dose (R488 and R565), but offer the vaccine at a lower cost to developing countries.
What would rolling out the vaccine involve?
This is also a two-dose regimen, with the second shot given after 29 days. This poses the same follow-up challenges as the Pfizer/BioNTech jab.
Although nowhere near the requirements of Pfizer/BioNTech’s candidate, this jab needs to be kept at -20C during transport and for long-term storage. For up to 30 days the doses can be kept between 2 degree Celsius and 8 degree Celsius, the temperature of a standard fridge. South Africa will probably not buy this vaccine owing to the transport requirements.
AstraZeneca/Oxford University
What were the results?
The preliminary data 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 regimen.
But an error – which was not initially disclosed by either party – resulted in some participants being given different dosages – a half-dose and a full dose a month later.
While they were never meant to receive the lower dose, the research team decided to continue the trial after discovering the mistake, Mene Pangalos, head of AstraZeneca’s non-oncology research and development, told Reuters.
Pangalos told the New York Times 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 refers to a statement from AstraZeneca’s spokesperson, which had been attributed to Oxford University, that says the mistake was due to a manufacturing error and had since been fixed.
The regimen showed 90% efficacy. Combining the results of the two different doses gives an average efficacy of 70%.
One possible reason for this higher protection rate is that the group that received the half-dose was roughly a third of the size of the other and had probably been followed up for a shorter period, meaning they may not have developed any Covid-19 symptoms yet.
Another limitation on the data is that those who received the half-dose were all under 55 and less likely to develop severe Covid-19, 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 24 November.
The company’s CEO, Pascal Soriot, told Bloomberg News it would be pursuing an additional global study to confirm the results seen in people who first received a half-dose.
How many Covid-19 cases were analysed?
A full analysis of the data has yet to be released. 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 vaccine, as well as between the two dosing regimens, have not yet been made public.
AstraZeneca’s statement also said the data from two different trials – in the UK and Brazil – were being combined in the analysis.
How soon will the shot be available?
AstraZeneca has announced it has begun seeking regulatory approval for its candidate. Although the countries to which it is submitting applications have not been disclosed, the vaccine will probably be approved by the UK or the European Union first. AstraZeneca will also apply for an emergency-use listing from the WHOand would require FDA approval to market its vaccine in the US.
What will it cost?
AstraZeneca and Oxford’s vaccine is the cheapest – a tenth of the cost of Moderna’s jab. The firm has already committed to being part of the COVAX agreement at between $2 and $3 (R30 and R45) per dose.
In June, AstraZeneca reached an agreement with GAVI and its COVAX partner, the Coalition for Epidemic Preparedness Innovations, to provide 300 million doses starting at the end of 2020 for $750-million, and 1 billion doses for low- and middle-income countries.
What would the rollout involve?
Like the other leading jabs, this vaccine involves two doses a month apart. This is a longer gap but presents the same logistical follow-up challenges.
Unlike its mRNA counterparts, this viral vector jab can be stored at between 2 degree Celsius and 8 degree Celsius. Given that this is the standard temperature at which most vaccines in South Africa’s childhood immunisation programme are kept, and that it does not need specialised cooling equipment, the AstraZeneca/Oxford candidate is the most accessible to developing countries so far.
As one of the trial sites, there is a higher likelihood that South Africa will be able to secure doses in recognition of its contributions to the results, but access to the shot is not necessarily guaranteed. The country’s involvement also means there will be data showing the safety and protection the jab can offer its population.
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 the first dose. Preliminary data show the efficacy could increase to more than 95% at 42 days after participants are first injected.
The data follow scepticism from researchers in the field about the validity and significance of the numbers because of the small sample group on which they were based.
How many cases were analysed?
Although the efficacy reported is on par with its peers, the sample group here is much smaller. The analysis includes 39 confirmed Covid-19 cases among the 40,000 participants. Of these, 31 had received the placebo and eight had been vaccinated.
Another interim analysis will be released once 78 Covid-19 cases have been observed.
How soon will it 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 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 from the WHO.
The Russian Direct Investment Fund (RDIF) is looking to have doses ready forrollout by March 2021.
What will it cost?
Although the cost is still unknown, the RDIF has committed to providing doses forless than $10 each.
What would rollout involve?
The jab is given in two doses, with the second given three weeks later.
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, eliminating the need for specialised storage equipment. DM/MC
This story was produced by the Bhekisisa Centre for Health Journalism.
