It may not be what the quarantine-weary public is imagining, but experts say the realistic expectation of a coronavirus vaccine would actually be an incredible step forward.
27 July 2020 (Chania, Crete) – Like the ancient mariner, the coronavirus refuses to leave us alone. Resurging in parts of the UK, but across Spain, and across America, it is still going to be around here when the winter comes. As we head indoors, it will be back for what most expect to be a dreaded second wave, disguised among a host of colds and flus.
Yes, vaccine trials look promising but we need a reality check. I was in some interesting Zoom chats over the weekend with the crews from the Milken Institute vaccine center and the Johns Hopkins University Coronavirus Center. The first coronavirus vaccine may arrive soon, but it’s unlikely to be the knockout punch you may be hoping for.
Why it matters: The end of this global pandemic almost certainly rests with a vaccine. Experts caution, however, that it’s important to have realistic expectations about how much the first vaccines across the finish line will – and won’t – be able to accomplish.
Where it stands: Work on a coronavirus vaccine is moving at an unprecedented pace. There are nearly 200 candidates in development, 27 are being tested in humans and a handful are already in an advanced phase of clinical trials.
• Each new bit of positive news out of that effort makes the pie-in-the-sky best-case scenario – that one of these products will prove out and win at least an initial nod from the FDA by early next year – seem more plausible.
Yes, but … First-generation vaccines often aren’t the ones that stop a new virus in its tracks, and experts’ hopes for an initial coronavirus vaccine are much more modest.
• Amesh Adalja, an infectious-diseases expert at Johns Hopkins University: “Right now, we just need something that’s going to mitigate the damage this virus causes. Maybe it doesn’t prevent you from getting infected, but it prevents you from getting hospitalized, or prevents you from dying. That would be huge.”
How it works: Some vaccines, like the one for measles, mumps and rubella, produce near-complete and long-lasting immunity. Others, like the annual flu shot, are important tools to help contain a virus but don’t achieve “sterilizing immunity.” A few points:
• It’s not yet known how much protection any of the potential coronavirus vaccines might provide, or how long it would last.
• Mark Poznansky, an infectious-disease specialist at Massachusetts General Hospital: “It’s hard to make vaccines against coronaviruses. It doesn’t mean its not possible but it is a challenge, especially with COVID-19, where we don’t yet understand the inflammatory response to the virus and what part of the immune response is critical to prevent infection.”
• While the initial evidence for COVID-19 vaccines seems promising, second- and even third-generation products will likely target more of the virus and, hopefully, generate stronger and longer-lasting immunity than the first few vaccines will offer, Poznansky said.
Vaccinating enough people to get safely back to our old, communal habits will also pose more practical challenges.
• Even with a jump start on manufacturing, which is happening now, there won’t be enough supply, at least at first, to address the sheer scale of a global pandemic. So we need some kind of system to distribute the global supply, and then to prioritize who in the U.S. gets our doses, as noted in a recent piece from Axios.
• And if distrust in a vaccine stops large numbers of people from getting it, then the U.S, may not achieve the “herd immunity” that prevents widespread outbreaks.
The leading candidates are drugs under development by Oxford University, the U.S. biotech firm Moderna and the U.S. pharmaceutical firm Pfizer. They require patients to get two shots. So if you want to vaccinate 300 million people, you’ll need 600 million doses. And getting 300 million doses will already be a tall order.
The bottom line: Even after a vaccine becomes available, the coronavirus may still hang around, infect and even kill people. The numbers would just be lower. That may not be what the quarantine-weary public is imagining, but experts say it’s a realistic expectation – and would actually be an incredible step forward.
POSTSCRIPT
Over the last few months I have spent a fair amount of time studying and researching COVID-19 and coronavirus in general. Two of my research staffers spend most of their time curating a tsunami of information. It requires parsing a mountain of data. The pandemic has left ordinary people debating case counts, positivity rates and hospitalization numbers in hopes of understanding the virus’s path.
Yes, this pandemic (all pandemics, really) are told in harrowing stories from hospitals, factories, nursing homes and meatpacking plants. But as this crisis stretches on, it is also unfolding in an increasingly complex spread of numbers. As I have noted in my series of posts about the COVID-19 pandemic (you can access my archive by clicking below) the problem is people are mixing and matching inaccurate statistics that measure different things and using this mish-mash to make irrational predictions. This has led to the weaponizing of false and misleading statistics.
In the next week or so I will post a perspective on what I have learned from my data analysis of this pandemic. But for this Postscript, a few points from my vaccine research which will augment the Zoom chat summaries above.
There is a story often told by vaccine experts about a vaccination process “gone wrong”. In 1976, when a mysterious new flu began spreading in the north-eastern United States a few months before the presidential election, President Gerald Ford raced ahead with a high-profile campaign to vaccinate the nation. The flu strain turned out to be rather mild – and the vaccine caused several hundred people to develop paralysing Guillain-Barré syndrome.
That debacle is also very central to the story of why the American public has such an uneasy relationship with vaccines if you read the “anti-vax” blogs. It’s also a precedent that worries the scientific community as it wrestles with how to deal with both vaccine hesitancy and overblown expectations for a potential coronavirus vaccine. Even the smallest, unwarranted cause for doubt, if badly mishandled, could deal a severe blow to the cause of global health. But so too could a failure to match the unmeetable expectations of a public desperate for good news.
Making it safe
The process for ensuring that vaccines are safe is well established and they are held to a much higher standard of safety than normal medicines. Inevitably, the safety bar is higher for vaccines than for drugs, because drugs you give to people who are already ill, vaccines you give to healthy people.
Many of the usual trial phases for vaccines are being run in parallel for COVID-19 candidates, but this is not cutting corners. Instead, the risk created is one of “process”, that the time and money spent on preparing for the next phase turns out to have been wasted.
The most advanced vaccine projects, including those of Oxford University and the US pharmaceutical company Moderna, are moving into large-scale Phase III trials in which any less common side effects or safety issues should become apparent. Side effects are common and can cover a wide range of ailments, most of which are unwelcome but not a significant barrier to receiving a jab. Some, however, might be so rare as to not emerge until there is population-scale deployment of a vaccine.
Maurice Hilleman, an American microbiologist who developed more than 40 vaccines, is said to have claimed that he only relaxed once the three millionth dose of a new vaccine had been given. That wasn’t without reason – these rare adverse effects can be serious. The 1976 case I noted above is only one example. Those of you in the UK reading this post will well remember Pandemrix, a vaccine for swine flu given to around six million people in the UK in 2009-10. It was found to cause narcolepsy, a debilitating sleep disorder, in around one in every 55,000 vaccinated individuals in the UK, or just over 100 people.
But the classic example which was given by the Johns Hopkins University team in the Zoom chat I noted above was RotaShield, a vaccine against diarrhea-causing rotaviruses released on the American market in the late 1990s. The vaccine was linked to a very small number of cases of intussusception, a life-threatening intestinal disorder, and was rapidly withdrawn from use. A replacement was not available for close to a decade and in that time hundreds of thousands of children died from diarrhea diseases that would have been averted had that so-called ‘bad’ vaccine been available.
The key point is that despite their phenomenal contribution to health, all vaccines carry some risk and it’s a societal decision, an ethical decision and a political decision about what the right balances of risks are, and that balance really depends on local circumstances.
The world is already mistrusting of vaccines, and we cannot roll out a vaccine to the whole world if it causes harm. Even if that harm is very limited and even if, as is expected, the benefit far outweighs the risk, it still has to be very clear what those risks are so that people have full knowledge of what they are undertaking, and understand for themselves the balance of benefit versus risk.
Constant vigilance and the battle with fake news
When drugs pass Phase III trials and enter widespread use, they are not simply forgotten about by regulators and scientists. Instead, a fourth phase – known as pharmacovigilance – is in place to monitor for and respond to any suspected adverse outcomes. In the case of a Covid-19 vaccine, that will be key to guaranteeing public trust.
Fake news is already out there. There is already stuff going around on social media saying that this vaccine was tested on children in Africa and they all died, it’s presented in a very emotional way, and once that’s out there it’s very difficult to fight that false information.
Once a vaccine is actually deployed, the risk of scares will increase risk perception – and not just from total fabrications. The Johns Hopkins team posited this:
Let’s say there’s a report of early pregnancy losses. It’s totally coincidental to the vaccine, but it gets reported as ‘this thing kills babies’ – and then suddenly people stop taking it. The only way to reassure people is to know that the surveillance infrastructure is there and to take vaccine safety seriously.
However, the unprecedented scale of any vaccination programme will create significant challenges and ethical questions. Any coronavirus vaccine is likely to be given to people who are not usually vaccinated and not normally monitored, such as healthy adults.
Likewise, while the UK and other developed nations have well-established pharmacovigilance systems in place, many poorer countries do not. That could lead to difficult questions – you might decide we won’t use that vaccine in Africa until we have got significantly more safety information from other countries, but in the meantime you might have protected thousands of people from getting the infection.
Whatever decision is made, none of these questions will be handled “willy-nilly” but it is essential that the public be made more aware of how they are debated if confidence in vaccines to be maintained.
A bumpy road to an inconclusive destination
Getting the message across to the global public that there is a vast network of regulation and monitoring behind the vaccine might also inject a dose of realism into public expectations. There is concern among many scientists that the media and political hype is building up huge expectations that will both undermine the fight against coronavirus and damage confidence in vaccines as a whole.
Not only is this going to be a slow process, but it’s also one with plenty of potential for setbacks and it could ultimately prove inconclusive. One of the most basic issues is that, while early trials have delivered positive results, a vaccine is still very far from being guaranteed to work.
But there needs to be someone out there explaining this. Because once those vaccines are tested on tens of thousands of people in Phase III trials, there is plenty of potential for failure.
One of the greatest setbacks could be caused by “antibody-dependent enhancement” (ADE), also known as disease enhancement or immune enhancement, a rare phenomenon in which the presence of antibodies in an individual can trigger a worse infection. Efforts to develop vaccines for Sars and Mers, two other coronaviruses, found evidence of ADE in animals.
In other cases, it has been a major setback. There was a case of a vaccine developed in the late 1960s for RSV, a common childhood illness, in which ADE was suspected as the cause of its failure. The vaccine was withdrawn from the market 51 years ago and we still don’t have a good RSV vaccine – and the reason is because of enhanced disease. It’s an issue that the entire Covid-19 vaccine community is keenly aware of – the safety of a Covid-19 vaccine is absolutely essential.
As I noted above, even if Phase III trials are passed with flying colors, manufacturing to scale could take a long time and there is always the possibility of a RotaShield-type event, which would call for a serious ethical debate. Just as concerning as safety issues is the still unanswered question of efficacy. It may be that, while candidate vaccines turn out to be quite safe, they aren’t anywhere near effective enough to be worth using.
Vaccines can have the very useful effect of reducing the severity of infection, but the holy grail for a coronavirus vaccine would be to prevent transmission as well. Given the still uncertain nature of immunity to COVID-19 and how long-lasting it is, that could be an unachievable goal.
If the immunity is short-lived then I think it’s a little bit futile because to mount a massive campaign every few months to vaccinate God and the world against this virus is not going to be sustainable. Such a vaccine would not be useless as it would protect the individual, but it’s a long way from the notion some seem to have that all we need is this one vaccine and the show is over.
More than just generating disappointment, scientists worry that over-hyped expectations for a vaccine risk creating serious problems. I’ll conclude with a member of the Johns Hopkins team:
For one they undermine the message that social distancing will be here for a long time and people need to maintain their efforts. It’s a marathon, not a sprint.