Covid-19 vaccines may not prevent people from getting severely sick or dying, it was claimed today.
Trials of hundreds of thousands of volunteers are investigating whether experimental Covid-19 jabs stop a person from picking up the infection.
But Professor Peter Doshi, the associate editor of the British Medical Journal, points out scientists are not waiting to see whether volunteers are protected from severe disease or death if they do catch it — which would only be the case if the vaccine didn’t work very well — before they are rolled out.
This is a particular concern for the elderly, who are the most at risk of severe Covid-19 outcomes, because the vaccine may not be as effective at protecting them from catching the coronavirus in the first place.
Vaccines typically do not work as well for those over the age of 60 because they have an aged immune system.
Professor Doshi, of the University of Maryland, also revealed that the studies will not prove transmission between people can be curbed. Scientists are not measuring if those who catch it pass it on to friends and family, regardless of whether they get sick themselves.
None of the front-runners — Moderna, Pfizer, AstraZeneca, Janssen, Sinopharm, or Sinovac — are measuring if their vaccines will save lives in their final stage trials.
But in response to Professor Doshi’s paper, scientists say there are ‘excellent’ reasons for running the trials, the main one being to speed up finding a vaccine which could otherwise take years because so few Covid-19 patients become severely ill.
Trials of hundreds of thousands of volunteers are investigating whether experimental Covid-19 jabs stop a person from picking up the infection. Pictured: Katelyn Evans receives a Pfizer’s experimental Covid-19 vaccine at Cincinnati Children’s Hospital Medical Center
A vaccine is considered key to ending the Covid-19 pandemic which has already killed 1.1million people worldwide. High hopes have been pinned on proving one works to cut the risk of the disease and stop it spreading.
The goal of finding a vaccine may seem fairly obvious to the public — to stop serious disease and death, and therefore damaging lockdowns.
‘Yet the current phase III trials are not actually set up to prove either,’ Professor Doshi said in his paper, questioning what a vaccine must prove to be considered ‘effective’.
Covid-19 vaccines may not prevent people from getting severely sick or dying, Professor Peter Doshi has warned
‘None of the trials currently underway are designed to detect a reduction in any serious outcome such as hospital admissions, use of intensive care, or deaths.
‘Nor are the vaccines being studied to determine whether they can interrupt transmission of the virus.’
There are 44 vaccines currently in clinical trials, according to the World Health Organization. Ten are in the final stages, called phase three, which are the final hurdle scientists need to tackle before one is proven to work.
Professor Doshi, an assistant professor of pharmaceutical health services research at the University of Maryland School of Pharmacy, Baltimore, said all ongoing phase three trials, for which details have been released, will end when a certain number of people have tested positive for coronavirus, including mild disease.
Scientists wait for a number of people to catch the coronavirus so they can compare whether the infection rates are higher in those who received the experimental Covid-19 jab, or in the placebo group.
If cases are higher in the placebo group, it would suggest that the vaccine protects against catching the coronavirus, in theory.
None of the phase three trials are waiting for endpoints of severe disease or deaths before stopping the trial, which would confirm the vaccine is indeed ‘life-saving’.
But Professor Doshi added: ‘A vaccine that has been proved to reduce the risk of symptomatic disease by a certain proportion should, you might think, reduce serious outcomes such as hospital admissions and deaths in equal proportion.’
Tal Zaks, the chief medical officer at Moderna, told the British Medical Journal that if the companies’ vaccine is shown to protect against mild disease, they will also be confident it protects against severe outcomes.
After all, the vaccine would have to be ineffective at preventing infection in the first place for a person to develop disease.
But Professor Doshi said this theory breaks down if vaccines are not equally effective in all ages.
And older people, who are most at risk of serious Covid-19, typically don’t respond to vaccines as well because their immune system takes longer to kick into action.
Professor Doshi said: ‘Whatever reduction in cases is seen in the overall study population (most of which may be among healthy adults), this benefit may not apply to the frail elderly subpopulation, and few lives may be saved.’
Children, immunocompromised people, and pregnant women have also largely been excluded from studies.
It is likely serious outcomes from Covid-19 are not being studied because it would take too long for a significant number of volunteers to actually get severely sick, given less than 10 per cent of people who catch it need hospitalisation.
It would need a lot more trial participants, and funding, to finish the trial as quickly as planned, if scientists were hell-bent on making sure the vaccine did not cause serious disease or death, the paper explains.
Professor Doshi said: ‘Hospital admissions and deaths from Covid-19 are simply too uncommon in the population being studied.
‘Final efficacy analyses are planned after just 150 to 160 “events,”—that is, a positive indication of symptomatic Covid-19, regardless of severity of the illness.’
|Moderna||Pfizer||AstraZeneca (US)||AstraZeneca (UK)||Janssen||Sinopharm||Sinovac|
|Prevention of symptomatic Covid-19||Yes||Yes||Yes||Yes||Yes||Presumed||Yes|
|Reduction in severe symptoms||No||No||No||No||No||No||No|
|Prevention of spread between people||No||No||No||No||No||No||No|
|Ages eligible||18+||12+||18+||5-12 and 18+||18+||18+||18+|
|Children and teenagers||Excluded||Many excluded||Excluded||13-17 excluded||Excluded||Excluded||Excluded|
|Pregnant or breastfeeding||Excluded||Excluded||Excluded||Excluded||Excluded||Excluded||Excluded|
WHEN WILL A COVID-19 VACCINE BE READY
There are high hopes a Covid-19 vaccine will be doled out, at least for the most vulnerable people, by the end of winter or early 2021.
But not every scientists holds that view, and some are reluctant to give false promises.
At the end of September, the optimistic chief scientific adviser said Britain could still get its hand on a coronavirus vaccine before Christmas.
In televised address to the nation on September 21, Sir Patrick Vallance said: ‘It is possible that some vaccine could be available before the end of the year in small amounts for certain groups.’
But Sir Patrick admitted it is ‘more likely’ that a vaccine — which is likely to require two doses to work — will be ready for the nation ‘over the first half of next year’.
Professor Jeremy Farrar, a member of the Scientific Advisory Group for Emergencies (Sage) and Wellcome Trust director, also believes a Covid-19 vaccine and effective treatment will be ready in the first quarter of 2021.
England’s chief medical officer Chris Whitty has erred on the side of caution. He has said a vaccine for the coronavirus may not be ready until next winter and that he’d be ‘surprised’ if we had one by this Christmas.
Professor Whitty told reporters on Saturday, August 12, it would be ‘foolish’ to plan for winter on the basis of having a vaccine but there was a ‘reasonable chance’ there could be one made available before the winter of 2021-2022.
He warned that going into winter there will be ‘real problems’ with Covid-19 and said that the country should plan on the basis of no vaccine being available.
Professor Peter Openshaw, from Imperial College London and an advisor to the Government’s Scientific Advisory Group for Emergencies, said in September he expected a nine-month gap between the vaccine’s discovery and it being made available to the public.
Because of this, he also doesn’t think a coronavirus vaccine will be available to the public until at least September 2021.
He told Sky News’ Sophy Ridge on Sunday September 13: ‘I do think that we will probably have a positive result of at least one of these vaccine trials, probably more than that, by Christmas.
‘And that means that with rapid scaling up we might have vaccination programmes that can roll out to some parts of the world in the next nine months.
‘Before the winter of 21/22 I hope that we should have vaccines that are effective.’
Trials will be able to report their final results once around 150 people show symptoms of the disease.
In Pfizer and Moderna’s trials, for example, individuals with only a cough and positive lab test would bring those trials one event closer to their completion.
Medscape’s Eric Topol has been a vocal critic of this, saying: ‘These numbers seem totally out of line with what would be considered stopping rules.
‘I mean, you’re talking about giving a vaccine with any of these programmes to tens of millions of people. And you’re going to base that on 100 events?’
Professor Doshi did not comment on the significance of efficacy if all 150 of the people who got symptoms were in the placebo group and none were in the vaccinated arm.
Moderna’s Tal Zaks said ‘too many people would die’ waiting to find out if Moderna’s vaccine prevented mortality.
Dr Andrew Preston, a reader in microbial pathogenesis who works in vaccines, University of Bath, agreed that it would cause too many delays.
He told MailOnline: ‘Covering every manifestation of Covid disease would require trials so large, that run for such long times, that they are very likely to be impossible to run and fund, and would delay the data so long that we’d be living without any vaccine-mediated intervention for years to come.’
Commenting on the BMJ editorial, Dr Preston argued there were ‘excellent and sensible reasons for running the trials as they are’.
‘To test vaccines in the very vulnerable would require vaccinating vulnerable people and then asking them to put themselves in situations in which they might be exposed to the virus.
‘The ethics of this would be highly questionable, so it makes sense to test whether the vaccine shows any effect in people who, if they did become infected, the consequences are far less severe.’
However, he agreed that it is important for there to be clarity on what vaccine trials will and will not show.
‘I suspect many [people] are wanting them to ‘return life to normal’ and so there needs to be careful consideration of what the various effects of the vaccines might be.
‘It’s been clear for some time now that an essential component of building the trust required for interventions to be effective, is transparency.
‘So it’s important that as we head towards the point when mass vaccination will begin, everyone is clear about what this will change in terms of restrictions, public health and disease.’
The prospect of a Covid-19 vaccine is edging nearer, with ministers and scientists alike claiming the first roll-out could be just after Christmas.
At the end of September, the optimistic chief scientific adviser Sir Patrick Vallance said Britain could still get its hand on a coronavirus vaccine before Christmas.
And Sir Jeremy Farrar, Sage scientific advisory group member and a director of the Wellcome Trust, has said at least one of a portfolio of UK vaccines could be ready by spring.
But other experts have waded in with a dose of realism, revealing that even if a vaccine is proven effective any time soon, it will be in limited supply.
The head of the country’s vaccine task-force Kate Bingham has previously admitted less than half of Britain will get vaccinated against Covid-19.
Experts say it is likely people will need two doses of each vaccine to be protected against the coronavirus. And those who are most vulnerable will be front of the queue.
WHICH VACCINES HAVE THE UK SECURED DEALS FOR?
1. GlaxoSmithKline and Sanofi Pasteur: 60million doses
The Government revealed on July 29 it had signed a deal with pharmaceutical giants GlaxoSmithKline (GSK) and Sanofi Pasteur
If the vaccine proves successful, the UK could begin to vaccinate priority groups, such as frontline health and social care workers and those at increased risk from coronavirus, as early as the first half of next year, the Department for Business, Energy & Industrial Strategy (BEIS) said.
Human clinical studies of the vaccine will begin in September followed by a phase 3 study in December.
The vaccine is based on the existing technology used to produce Sanofi’s seasonal flu vaccine. Genetic material from the surface protein of the SARS-CoV-2 virus is inserted into insect cells – the basis of Sanofi’s influenza product – and then injected to provoke an immune response in a human patient.
2. AstraZeneca (manufacturing University of Oxford’s): 100million
AstraZeneca, which is working in partnership with Oxford University, is already manufacturing the experimental vaccine after a deal was struck on May 17.
Professor Sarah Gilbert, who is leading the Oxford team, is confident the jab could be ready for the most vulnerable people by the end of the year.
Her comments came after the results from the first phase, published in The Lancet on July 20, showed promise.
The team have genetically engineered a virus to look like the coronavirus – to have the same spike proteins on the outside – but be unable to cause any infection inside a person. This virus, weakened by genetic engineering, is a type of virus called an adenovirus, the same as those which cause common colds, that has been taken from chimpanzees.
3. BioNTech/Pfizer: 30million
US drug giant Pfizer – most famous for making Viagra – and German firm BioNTech were revealed to have secured a deal with the UK Government on July 20.
It reported positive results from the ongoing phase 2/3 clinical trial of one called BNT162b1 on July 1. The company is still running phase 2 trials at the moment.
Pfizer’s vaccine is one called an mRNA vaccine, which do not directly inject bits of the virus into the body but send genetic material.
mRNA vaccines programme the body to produce parts of the virus itself by injecting the body with a molecule that tells disease-fighting cells what to build. The immune system then learns how to fight it.
4. Valneva: 60million
The Government has given Valneva — whose vaccine is understood to be in the preclinical stages of development — an undisclosed amount of money to expand its factory in Livingston, Scotland.
While the Government revealed a 60million dose deal on July 20, the company said it had reached agreement in principle with the UK government to provide up to 100million doses.
Valneva’s jab is an inactivated whole virus vaccine, meaning it injects a damaged version of the coronavirus itself into the body.
The virus has been destroyed in a way that makes it unable to cause infection, but the body still recognises it as a dangerous intruder and therefore mounts an immune response which it can remember in case of a real Covid-19 infection.
5. Janssen (Johnson & Johnson): 30million
The Government has agreed to buy 30million doses of a vaccine made by Janssen if it works.
Officials have agreed to help the company in its development of the jab by part-funding a global clinical trial. The first in-human trials of Janssen’s jab began in mid-July and are being done on adults over the age of 18 in the US and Belgium.
The jab is named Ad26.COV2-S, recombinant, and is a type of jab called a viral vector recombinant vaccine.
Proteins that appear on the outside of the coronavirus are reproduced in a lab and then injected into the body to stimulate an immune reaction.
The ‘Ad’ part of the vaccine’s name means it works using an adenovirus – a virus best known for causing the common cold – as a vehicle to transport the coronavirus genetics into the body.
6. Novavax: 60million
Britain has ordered 60million doses of a vaccine being developed by the US-based company Novavax. It will help to fund late-stage clinical trials in the UK and also boost plans to manufacture the vaccine in Britain.
Novavax’s jab, named NVX-CoV2373, showed positive results in early clinical trials.
It produced an immune response in 100 per cent of people who received it, the company said, and was safe and ‘generally well-tolerated’.
Novavax’s candidate is also a recombinant vaccine and transports the spike proteins found on the outside of the coronavirus into the body in order to provoke the immune system.
7. Imperial College London: Unknown quantity
Imperial College London scientists are working on Britain’s second home-grown hope for a jab. The candidate is slightly behind Oxford’s vaccine in terms of its progress through clinical trials, but is still a major player.
The UK Government is understood to have agreed to buy the vaccine if it works but details of a deal have not yet been publicised.
Imperial’s jab is currently in second-phase human trials after early tests showed it appeared to be safe.
Imperial College London will try to deliver genetic material (RNA) from the coronavirus which programs cells inside the patient’s body to recreate the spike proteins. It will transport the RNA inside liquid droplets injected into the bloodstream.