Last Wednesday evening, shortly after announcing yet another round of restrictions, effectively cancelling Halloween and raising a big question mark over Christmas, Micheál Martin quietly disclosed how bad he feels things are.
“Until we get a vaccine,” the Taoiseach told yet another hastily arranged press conference in Government Buildings, “normal life will not resume as we know it”.
With the Government’s version of the “test, trace, isolate” strategy failing to rein in infections, and no official enthusiasm for alternative strategies such as elimination of the virus or shielding of the vulnerable, its hopes of getting out of this crisis are increasingly reliant on vaccines being developed to protect against the disease.
With one-third of the world’s population enduring quarantine this year, 1.2 billion children taken out of school and $1 trillion wiped off the value of the global economy, it’s not just Ireland that is crying out for a solution to Covid-19.
If 2020 was the year of the pandemic, 2021 is shaping up to be the year of the vaccine. Hundreds of vaccines are in development, 11 are already at phase three, being tested on thousands of humans, and the first three products are forecast to be ready by the end of this year.
Yet this next stage of the pandemic brings with it a new set of questions and unknowns. Will the vaccine – or vaccines – work? Will they work on those most at risk? Will they be safe? Will sufficient people use them, in order to provide wider population protection? Who gets them first? How much opposition will they encounter?
At this stage, it can be assumed, given the massive resources being thrown at the problem, that at least some of the 170 vaccines under development will make it through to regulatory approval, probably in the next six months. Demand for the protection they afford is likely to be strong.
Equally, it is likely there will be opposition to whatever vaccine is produced, in particular if it is mandated (ie compulsory). The prospect of a global Covid-19 vaccine has breathed new life into the traditional anti-vaccine lobby, which has found common cause with anti-lockdown and anti-face mask groups.
“There’s no doubt, this is going to be contested,” says one doctor, who declines to be identified because of the “toxic” atmosphere around the issue. “There’s a huge amount of hostility out there, online. You’ve got anti-mask, anti-lockdown, anti-5G, soon it will be anti-vaccine. Others will oppose a vaccine for Covid simply because Donald Trump supports it.”
It’s like watching the Grand National: you never know if someone is going to fall at the last fence
There is nothing new about disinformation around pandemics and vaccines. During the 1918 flu pandemic, for example, the false rumour went around that the virus was being spread by people taking aspirin, made by the German company Bayer. To this day, attempts to eradicate polio have been frustrated in some countries by claims the vaccination programme is a western plot.
Variety of approaches
The new vaccines under development take a variety of approaches to the challenge of instructing the immune system to mount a defence against the SARS-CoV-2 virus. Some build on existing technologies; others are following novel routes and may take longer.
According to Prof Karina Butler, infectious diseases specialist and chairwoman of the National Immunisation Advisory Committee, there is “every hope” that one or more of the vaccines in development will prove effective.
“We are progressing more quickly than ever before. But it’s like watching the Grand National: you never know if someone is going to fall at the last fence.”
This is because each candidate vaccine has to jump through numerous hoops before it can hope to get approval. Is it effective? Is it safe? Does it work with at-risk groups?
Those vaccines that have reached phase-three trials – using a far larger testing group than phases one or two – are each being tested on thousands of adults, and could ultimately be used by billions of the world’s population. Because the trials are randomised, not all participants are actually getting the vaccine; some are given a placebo.
Prof Butler says phase-three trials give good data in terms of common or even relatively uncommon problems that can arise. Indeed, a number of prominent trials have been halted in recent weeks after participants fell ill.
However, they may not pick up every rare side-effects of a vaccine, she points out, so some level of risk is involved. Children, older people, pregnant women or other groups could react differently to the vaccine, for example.
The aim is to address any issues that arise in final trials and in surveillance after a vaccine is approved by regulatory agencies such as the European Medicines Agency and, in Ireland, the Health Products Regulatory Authority (HPRA).
At this stage, Prof Butler says, it is a “big ask to look into the crystal ball” and assess which of the candidate vaccines offers the best prospect of protection as well as a ready supply.
The speed at which the new vaccines are being developed has caused some unease. Most take 10 to 15 years to bring to market and even the fastest in development – for mumps – took four years.
Regulators have set the bar for the primary endpoint of a phase three at 50 per cent protection, meaning that an effective vaccine is considered one that cuts the number of infections among those receiving the vaccine by half.
“The reason they’re going so fast is because they’re doing so much in parallel, rather than in sequence, and that has never happened before with vaccines,” says UCC biochemistry lecturer Dr Anne Moore. “Looking at safety, it will take as long as it takes.”
Speaking at a symposium on vaccines organised by the Royal College of Physicians in Ireland (RCPI) on Wednesday, Dr Moore said she would have “no qualms” about getting any of the new vaccines once they are properly approved. “I’d be first in the queue to get them.”
Also speaking at the RCPI event, Prof Luke O’Neill, a biochemist at Trinity College Dublin, said, “There’s never been a spotlight on vaccine development like this. Big Pharma is aware it’s being scrutinised hugely. The big fear is if there is a safety signal, it will stop people vaccinating for other diseases. So safety is the absolute top priority here.”
I don’t think a vaccine will end this pandemic tomorrow, or suddenly; it is going to trickle on for a little while
The fact that a number of trials have had to be stopped due to adverse patient events is “a good sign”, he said.
Liz O’Brien, a former pharmaceutical regulator who has also worked in drug development, warns that while regulatory bodies work “to the highest scientific rigour, a vaccine with an efficacy as low as 50 per cent is not a panacea and cannot form the basis of Ireland’s Covid strategy”.
“We know that efficacy is often lower again in older populations, and that must be considered in the overall picture of strategic planning.”
Dr Moore also expressed concern about a vaccine working for older people unless it is very efficacious. And she cautions: “I don’t think a vaccine will end this pandemic tomorrow, or suddenly; it is going to trickle on for a little while.”
Initially, Prof Butler says, it is likely a successful vaccine will be licensed for those most at risk – healthcare workers, for example, or, if suitable, older people.
The extent to which vaccines provide protection varies from person to person according to our make-up and immune response. The flu vaccine, for example, is generally less effective in older people with depleted immune systems.
Vaccines, though, also provide wide protection across the population, provided enough people take them. For a highly infectious disease such as measles, for example, a threshold of 95 per cent uptake has to be reached in order to achieve herd immunity.
Most people will hesitate when presented with something new, especially if they don’t feel they are at risk
Given how transmissible Covid-19 is, it is thought an uptake of at least 60 per cent, and preferably much higher, will be needed to confer population protection.
But is this level of cover achievable? In a recent RTÉ poll conducted by Behaviour & Attitudes, 32 per cent of people said they would be unlikely to take a new Covid-19 vaccine, while 56 per cent said they would; 12 per cent didn’t know.
Prof Butler says she understands the sentiment expressed in the poll.
“Most people will hesitate when presented with something new, especially if they don’t feel they are at risk. I’m fairly confident we’ll have solid safety data before we go recommending to people to take a particular vaccine.”
Some of the products in development build on existing vaccine platforms, she points out, making it easier to make an informed choice.
“There will always be a core group who don’t want vaccines no matter how much data there is on them,” says Butler. “They tend to be a small minority, but the wider group of people looks at the pros and cons and aims for the best thing for them.”
It is less than a decade since anti-vaccine campaigners began targeting the then new HPV vaccine for teenage girls. Using social media to deliver an emotion-laden message directly to parents, they claimed hundreds of girls had suffered chronic ill-health after taking the cervical cancer vaccine.
Despite the absence of any evidence of a causal link between the girls’ symptoms and the vaccine, uptake of the vaccine plummeted from 87 per cent to 50 per cent, as vaccine hesitancy grew.
It took a sustained response from medics, pro-vaccine advocates and the likes of Laura Brennan, the young Clare woman who became the poster girl for the HPV vaccine before succumbing to cervical cancer, before rates started rising again.
The issue died away, but rumbles on. Regret, the group set up by parents alleging harm from the HPV vaccine, told The Irish Times this week “many” of their daughters “remain in chronic ill-health” and that “many cases have been lodged with the courts”.
“We have concerns that a rushed ‘warp speed’ vaccine, which has not undergone long-term testing or testing for non-specific effects, may not meet the necessary safety standard,” the group said in a statement.
Today, the controversy around Covid-19 has breathed new life into the anti-vaccine cause. Information sheets have been dusted down, websites spruced up and, across Europe and the US, people have taken to the streets.
On an overcast Saturday afternoon earlier this month, those opposed to a vaccine were prominent among the anti-lockdown protesters outside the Custom House in Dublin.
“Stick your vaccine up your arse,” one of the musicians playing at the rally shouted, to general amusement in the crowd.
The rally was jointly organised by Health Freedom Ireland (HFI), a group composed of longstanding vaccine sceptics that says its mission is to provide “impartial information” on the issue.
We have been accused of being far left and far right but we have no political agenda
Co-founder Maeve Murran told the rally HFI’s aim was to “inform, educate and support people around vaccines and freedom of choice”.
“We have been accused of being far left and far right but we have no political agenda. We are committed to the provision of truth through the dissemination of legitimate scientific information,” she said.
The group responded at length to questions from The Irish Times and published the answers, with footnotes, on its website.
It claims “many parents” are highly concerned about the number of vaccines recommended for their children, that “many Irish children” are suffering side-effects and that “transparency and unbiased information is not always forthcoming from either the HSE or our healthcare professionals”.
“The development of Covid-19 vaccines shines a spotlight on many of the existing issues we have with other vaccines, especially in relation to the definition of ‘safety’ and the definition of ‘effective’ in clinical trial protocols,” it says.
Though many of the arguments made by the group seem familiar, and are certainly vaccine-sceptical, the group rejects the “anti-vaxxer” tag. “The term anti-vaccine is neither useful nor correct. It is often deliberately used to discourage and discredit those that dare to raise valid concerns over vaccine safety and efficacy.”
Science writer David Robert Grimes, a prominent critic of the anti-vaccination movement, describes HFI’s information on vaccines as “a trove of well-trodden anti-vaccine propaganda, giving the illusion of rigour without any substance”.
“It tells us that vaccines contain formaldehyde like that’s an alarming fact – in reality, there’s a maximum of 0.1mg in a vaccine, versus about 6mg in an apple. It also makes the discredited claim that there is a link between vaccines and autism, which there most certainly is not.
“The leaflet hand-waves away the copious evidence for the efficacy of vaccination garnered over centuries as a mathematical abstraction.
“There has always been an anti-vaccine cohort, since [Edward] Jenner [creator of the smallpox vaccine],” says Grimes, whose book The Irrational Ape explores the decline in trust in science and the rise of misinformation. “But they’ve always been a vocal but small minority, because the success of vaccines has been so blindingly obvious for the most part.
“The problem is that people lose sight of how important vaccines have been for our societal health. Immunisation has made diseases such as polio or smallpox spectres of the past, so we don’t have this visceral reference point and [we] sometimes take vaccines for granted or become complacent.”
This is not new bullshit, it’s the same old bullshit. They running the same myths, using the same playbook
Grimes says the other factor driving the increased visibility of anti-vaccine groups is their early mastery of the internet.
“While small, they have been absolute pioneers in dominating the internet, they were quick to spot its potential and, later, that of social media.”
As humans, most of us are prone to responding more to emotive or negative statements over sober analysis, and the anti-vaccine movement has effectively exploited this form of negativity bias, he says.
With the World Health Organisation identifying vaccine hesitancy as one of the top 10 threats to public health globally, Grimes says the main driver of this trend is exposure to anti-vaccine conspiracy theories online.
There is “nothing new” about objections raised by the anti-vaccination lobby to a Covid-19 vaccine, says Grimes. “This is not new bullshit, it’s the same old bullshit. They running the same myths, using the same playbook with every vaccine.”
Last year, then minister for health Simon Harris floated the idea of requiring children to be vaccinated before admission to creche. The idea never progressed, but mandatory vaccination is likely to feature next year in the debate around a Covid-19 vaccine.
Prof Butler says mandatory vaccination is best used “as a last resort and only in specific situations”.
“The first step with a vaccine should be to incentivise and make it easy for people to take it, to remove barriers and provide education.”
Recent improvements in the uptake of the flu vaccine in healthcare workers and the general population show how this approach can work, she says.
“A lot of groundwork on vaccine hesitancy will pay dividends. But we have to be responsible about this and make sure it is safe. And if a person suffers harm, there should be a mechanism to support them.”
“Mandating is not the way forward,” according to Dr Moore. “It has to be by consent.”
A “better policy”, Prof O’Neill suggests, could be “to say ‘you’re part of our society and if your child is not vaccinated you can’t go to school or, if you don’t have an immunity stamp on your passport, you can’t travel.’”
Grimes says he understands the apprehension of some about the speed with which a Covid-19 vaccine is being developed. “The reason we do phase three trials is to test for safety, to ensure it’s causing more good than harm. It’s about balancing the risks with the benefits.”
People get tangled up in seat-belts in car crashes at times but we still use them because of the enormous safety benefit they confer, he points out.
“We’re currently seeing what life is like without a vaccine. It’s desperately true that we need something to be able to live life again.”