Since much of the world remains at home because of the coronavirus, many people have hoped for a major economic reopening on a vaccine. With more than 100 vaccine candidates for Covid-19 in production things seem to look up – and the conventional wisdom, often adapted by White House officialsis that this medical delay can come in 12 to 18 months. Secretary of Defense Mark Esper outright promised that “we will deliver a vaccine to scale by the end of this year to treat the American people and our partners abroad.”
But some experts warn that even 12 to 18 months may be optimistic for a Covid-19 vaccine: the previous record getting a vaccine was four years, and a cliché in the field is that vaccine development is measured in years, not months.
That is not to say that the chance of a commonly available vaccine is zero in 12 to 18 months. But they are also not 100 percent. Amesh Adalja, a senior scientist at the Johns Hopkins Center for Health Security, told me that the 12 to 18 month timeline is “very ambitious”. Kendall Hoyt, a vaccine and biosafety expert at Dartmouth, told me it will be challenging, but perhaps doable: “We could conceivably have something in that timeline – if all goes well.”
There are two major problems. First, it is not clear whether a vaccine can even be developed; It is possible – as is the case with other pathogens, such as malaria and HIV – that even the world’s best scientists never crack the Covid-19 coronavirus.
Second, even if a vaccine candidate is promising, time is a necessary part of this line of research. Scientists need months to assess not only whether a vaccine confers immunity for months, but also whether it is safe, as side effects can show up weeks or months later. Safety also has important public health implications: Any damage from a Covid-19 vaccine can be used by anti-vaccination advocates, who have already spread their message, even with the facts against them, to perpetuate their agenda.
Even without a vaccine, there is still a chance that other scientific and medical innovations will come around that make Covid-19 significantly less dangerous, even if they don’t cure it outright. Advances in treatment, along with enough health care capacity to see all infected patients (still a work in progress), could end at least some social distance, even if a vaccine doesn’t.
And some experts still hope that a vaccine will come soon. “I’m optimistic,” Natalie Dean, a biostatistics professor at the University of Florida, told me. “There is so much work being done in parallel.”
But a vaccine rescuer may not come as soon as we all hope. For policymakers, this means that more attention should be paid to other medical treatments and a vaccine, and that other measures, such as testing and tracking, should be encouraged, allowing states to somewhat ease social distance even without a vaccine. For the general public, it means preparing to stay at home to some degree longer than they would like.
Vaccines really take time
Experts emphasized that vaccine development takes a lot of time – and that’s not just due to bureaucratic hurdles or overly cautious measures.
Firstly, a vaccine candidate must be discovered, which can be validated as real by research. This alone takes a lot of work, and scientists are still tinkering with different types of vaccines – some of which have never been successfully developed and used in humans – to see what can work with Covid-19 and other types of viruses. This can range from the traditional vaccine, which uses an attenuated version of a virus to boost immunity, to newer types of vaccines, such as the potential use of messenger RNA to try to more accurately trigger an immune response. (For more information on the different types of vaccines I highly recommend Derek Lowe’s report on the subject in the journal Science.)
Whether a truly successful vaccine candidate is developed is the first major hurdle. “Things can fail for several reasons,” said Hoyt. “Something that may look promising in the lab may not behave in a human body as we expect it to.”
This does not only apply to vaccines: A 2017 analysis in PLOS One found that less than 10 percent of the drugs that entered clinical trials between 2006 and 2015 were ultimately approved by the Food and Drug Administration. So for every 10 articles you see about promising new drugs, nine of those drugs are likely to fail.
Other experts are more optimistic on this front. Adalja noted that there is one coronavirus vaccine for cows – not for the SARS-CoV-2 virus that is hiding people today, but for another type of coronavirus. That gives Covid-19 vaccines better chances than HIV vaccines, Adalja argued, “I don’t think the same hurdles that apply to the HIV search are even close to the search for the coronavirus.”
Even if we get a promising vaccine candidate, it will take time to make sure the candidate is safe and effective. Researchers take months to ensure long-term immunity, while ensuring that the vaccine doesn’t cause unpleasant side effects that, although usually in rare cases, can make healing worse than the disease.
And if a vaccine candidate passes all of this testing and manufacturing, that’s not the end of the challenges. This is a vaccine that the whole world wants. “There will be a capacity problem because a large percentage of the world’s population needs a vaccine,” said Hoyt. “You just don’t get enough. Vaccine companies are not built to produce enough vaccines for the world in a short time.”
Stuart Thompson at the New York Times analyzed the many steps a vaccine candidate needs to reach the real world: academic research, preclinical work, three phases of testing, factory building and production and distribution. From the first to the last point, a vaccine can last up to 16 years.
Fortunately, there are ways to speed that up. Some of these steps can be done in parallel. Public and private entities can now start building vaccine factories, as Bill Gates has already promised. Human challenge studies, in which healthy people are directly exposed to the virus, may help test for immunity more quickly (although some people in the field are skepticalbecause setting up these trials may take longer than more traditional studies).
Even without trials of human challenges – which can raise real ethical concerns if there is no cure for the virus that infects humans – there is reason for optimism in this area too: because coronavirus is already around the world, immunity testing in the real-world settings (unfortunately) will not be difficult. This is not so easy with some viruses; Dean pointed out that this was very difficult for the MERS vaccine because the virus was not widespread. “It is so rare,” she explained. “That’s no problem here” with Covid-19.
According to Thompson’s analysis, if every step is accelerated successfully, we may get an emergency vaccine by February 2021 and be fully distributed by the end of that year. But again, those are big ifs – assuming many bets pay off in the end.
“It would be remarkable to find a working vaccine during that time,” Hoyt said. “It would be something to be very proud of. In that time frame, having enough of that vaccine for everyone would be a miracle. ‘
There are real risks of rushing a vaccine
Aside from the inevitable time constraints, there are good reasons why vaccines take a long time to develop and spread: Without months or even years of evidence, there may not be enough evidence that a vaccine works as promised. That can give people a false sense of security or cause dangerous side effects later on.
There is good reason to be careful with Covid-19. In the New England Journal of Medicine, experts at the Coalition for Epidemic Preparedness Innovation warned that vaccine trials for the coronaviruses SARS and MERS “raised concerns about exacerbation of lung disease, either directly or as a result of antibody-dependent improvement.”
But one of the reasons these vaccines had to be so safe is because the researchers and manufacturers behind them followed strict scientific standards. They made sure that these drugs produced lasting immunity without major side effects. They ensured that the vaccines were produced under safe conditions and without contamination. They made sure that the people who gave the vaccines were well rested and trained. These things can be considered obstacles, but they are there to protect people.
If these steps are not followed correctly, there is a real risk. In 1976, America ran outside a vaccine in response to fears of a widespread swine flu outbreak. It turned out that the Mexican flu that year was not as widespread as officials feared, and the improperly tested vaccine led to a rare neurological condition called Guillain-Barré syndrome, in 450 people. “It caused more damage than it saved,” Josh Michaud, Deputy Director of Global Health Policy at the Kaiser Family Foundation, told me.
Vaccine production has come a long way since 1976. But it has come a long way, in part because we have regulations and safeguards to try to ensure efficacy and safety, and that protection may now come after a cure after the 12 – up to 18-month window.
And mistakes are still happening, such as a European H1N1 flu vaccine increased the risk of narcolepsy.
The potential damage here is not only on a personal but also a social level. If a Covid-19 vaccine leads to bad side effects, some experts feared that anti-vaccination groups – who already have concerns about the disease, even if the facts are not on their side – could take advantage of the problems to get their message across spreading. That would be a public health disaster.
“We’ve already seen anti-vaxxers building up against the vaccine we don’t even have yet,” Tara Smith, an epidemiologist at Kent State University, told me. “I am thrilled that we should do this as soon as possible, but not cut back on any of the safety mechanisms in any way.”
However, the risks of rushing must also be weighed against the reality that people are currently facing. Covid-19 kills hundreds of thousands of people around the world. It forces places to shut down their economies and individuals to stay at home. This causes damage not only from job losses and income, but also from activities that help preserve people’s mental health and happiness. There may be a risk of damage from a hasty vaccine, but keeping the world trapped in its current state also carries risks and damage.
It is a balancing act. And we may not know if we’ve got the right balance until a vaccine is out in the world for a few months or years, giving researchers time and data to see if it’s really safe and effective.
“Everything is a cost advantage,” said Hoyt. ‘Going to the supermarket is not without risk at the moment. What risk do you prefer? ‘
Other medicines and efforts can help fill the void
At the same time, humanity does not necessarily have to rely on a vaccine to get us out of the current situation.
The story of HIV is educational. While a safe and effective HIV vaccine has eluded humanity for decades, we have developed antiretrovirals that can fight HIV so well that it is undetectable in the body – even preventing its spread – and other treatments that help it is much less likely that someone will catch the virus from someone who is HIV positive. People were now treated for HIV early can live that long as their HIV negative peers. There are many differences between HIV and the coronavirus, but this shows that there are alternatives to a vaccine.
With coronavirus, research into non-vaccine treatments is still in its infancy. So far, results have been mixed with remdesivir and disappointing with hydroxychloroquine. But again it’s early so there could be a big break between the 280-plus non-vaccine therapeutics currently under investigation. Aside from a blockbuster, a new trial in hospitals and clinics could at least help treat Covid-19 patients much more effectively and safely.
The downside, however, is that producing these alternatives can take weeks or months. “We need more time,” an infectious disease epidemiologist, Saskia Popescu, told me. “It will take a while before we really understand some medical procedures that do and don’t work.”
Other medications and treatments can also help make a vaccine. If one of the concerns in, for example, human challenge studies is that they will expose people to a virus that cannot be treated, that concern will be clearly alleviated if there are drugs that can effectively treat Covid-19. That could open the door to more aggressive ways to test a vaccine, accelerating its development and introduction.
Outside of treatment, there are also public health interventions that could help fight the coronavirus without a vaccine. Other countries, such as South Korea and Germany have aggressively deployed comprehensive testing and contact tracking to isolate infected people, quarantine their contacts and deploy community-wide efforts, such as lockdowns or other forms of social distance, if needed. These measures alone are not enough to restore life to normal – such as South Korea and Germany are learning – but they make it much easier, experts say, to extinguish embers before they become wildfires.
Again, this takes time – probably more than it should. The US has made some progress in more tests in recent weeks, but the vast majority of states still do not have enough.
These public health interventions and the prospects of non-vaccine medications are not the best possible outcome – a vaccine still holds that claim – but they may offer some relief. As people continue to get tired of it at home, the reprieve and hope that the alternatives offer can help save time for a vaccine to arrive – whether that takes six months or many years to come.