Why a vaccine may not be enough to end the pandemic

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Without a vaccine or treatment, the world has been forced to adopt severe tactics to slow the spread of Covid-19: social distancing, shutdowns, closures, and cancellations. As states in the US begin to reopen, it’s clear there is still much hardship to come — for those laid off, for businesses forced to implement costly new health measures, for those still at risk of infection.

But the global race to develop a Covid-19 vaccine to shield people from the infection is now well underway, and gaining ground by the week. There are now more than 150 vaccines under development from governments, nonprofits, and private companies. Several are in stages of human clinical trials. Some of the developers, including a research group in China and the US biotech firm Moderna, have already posted preliminary but promising results from their vaccine trials.

“This is an extraordinary time we’re living in right now,” said Anna Durbin, a vaccine researcher and a professor of international health at the Johns Hopkins School of Public Health. “The pandemic is motivating a lot of [vaccine] efforts around the world.”

Yet as tempting as it is to predict how the vaccine will fit into the great epic of Covid-19, it’s impossible to know exactly how it will play out.

The kinds of vaccines we get and how well they’re distributed could determine whether this virus will fade away or will linger forever. And many of the decisions that could affect those outcomes are being made now.

There are four key elements that will determine how a vaccine will play out — how effective it will be, when it will be ready, how much of it would be available, and what the world does in the meantime to limit Covid-19. Here are some of the possibilities, and how they could change the course of the pandemic.

Efficacy: Will the vaccine grant lifelong immunity, or will immunity weaken in a few years?

A vaccine is a drug that primes the immune system to fight off an infection from a specific pathogen, protecting the recipient from a future infection.

Given the number of trials underway, some researchers are optimistic that not just one, but multiple Covid-19 vaccines will likely come to fruition. But the amount of protection they provide could vary. On the high end of possibilities, the vaccine could provide what’s called “sterilizing immunity,” meaning the recipient would be safe from infection potentially forever. This would be along the long lines of the smallpox vaccine.

Then there are lesser degrees of protection that could allow the virus could take root but the vaccine would coach the host’s immune system to fight it off before it can do too much damage. The inoculated could experience mild symptoms and transmit the disease, but the vaccine would prevent the more dangerous outcomes. This is how some influenza vaccines work.

One variable shaping efficacy is how quickly the virus mutates. A faster rate of mutation would increase the likelihood that the vaccine would not generate an effective immune response to the virus. SARS-CoV-2, the virus behind Covid-19, is a single-stranded RNA virus. Such viruses are notorious for high mutation rates, but those mutations don’t necessarily occur in a way that would weaken protection from a vaccine.

“Measles is also a single-stranded RNA virus. It mutates a little but it doesn’t mutate away from the vaccine,” said Paul Offit, director of the Vaccine Education Center at the Children’s Hospital of Philadelphia. “I think that you’re not going to need to do what you do with influenza where you have to get a yearly vaccine. Influenza is a moving target. That’s not going to be this virus.”

In fact, evidence seems to show that SARS-CoV-2 may have a relatively slow mutation rate for an RNA virus, increasing the chances that a vaccine would offer long-term protection.

“On the other hand, the vaccines will likely induce immunity that is short-lived and incomplete,” Offit said.

That is, the vaccine will likely offer protection that lasts a few years rather than decades or the near-lifetime immunity granted by some vaccines for other viruses.

And by “incomplete,” Offit explained that the vaccine would likely prevent the most severe manifestations of Covid-19, but it would likely do little to stop asymptomatic infections or milder forms of the illness.

This theory is based on what scientists have learned from how people have responded to other coronaviruses and how long people have retained immunity after an infection or a vaccination. For instance, people can get reinfected by the coronaviruses that cause the common cold within a couple of years of their first infection.

It’s not clear yet that surviving Covid-19 creates immunity to future infection. Even if it does, there’s isn’t a good way to tell how long that immunity will last besides waiting and seeing if survivors are susceptible again. That means it’s hard to gauge how long immunity will last from a vaccine at this point either.

The effectiveness of the vaccine can also vary for different groups. The shingles vaccine, for instance, is recommended for people over 50 years of age because they face higher risks of severe illness from the virus. The influenza vaccine has a different formula for people over the age of 65.

It may be the case that one type of Covid-19 vaccine is recommended for some age groups or people with preexisting conditions, while another type of vaccine is deployed to the general public. If immunity fades over time, people will need periodic boosters or revaccinations. And some people’s immune systems may not respond to the vaccine at all. “There may be people out there who are fundamentally unvaccinatable,” said Benjamin Neuman, a virologist at Texas A&M University Texarkana.

Timing: How soon until scientists find a vaccine that works?

A lot can change between now and whenever a vaccine for Covid-19 will become available. It may be months, it may be years — it’s not clear how long it will take, and that has huge implications for public health decisions we make in the meantime.

There is a global effort underway to speed up vaccine development. Governments are making efforts to fast-track funding and regulatory approvals, like combining phases of clinical trials. Companies are also putting their own researchers on the task. Nonprofit groups and philanthropists are also chipping in. That’s why some researchers are optimistic that a Covid-19 vaccine could arrive in record time. “This is as accelerated as it gets,” Offit said.

But the history of vaccine development shows that it can be a long, frustrating process. For instance, the mumps vaccine holds the record for fastest development time, which was four years. Most vaccines have taken much longer, often more than a decade.

The timing of when a vaccine comes out is critical because it determines the landscape where a vaccine would be released. Within the next two years, odds are Covid-19 will have spread, but the vast majority of the world’s population would still be unexposed and vulnerable to infection.

“A lot of optimism is swirling around a 12- to 18-month time frame, if everything goes perfectly,” Rick Bright, the former head of the Biomedical Advanced Research and Development Authority, told lawmakers in May. “We’ve never seen everything go perfectly. I think it’s going to take longer than that.”

As time goes on and the virus spreads, more people in a population will have been exposed to the virus, so fewer doses of the vaccine would be needed. The massive trade-off is that allowing the virus to spread further would come with more deaths and strain on the health care system.

A longer wait for a vaccine could mean increasing fatigue from pandemic control measures. Lockdowns and stay-at-home orders have already proven to be immensely costly and controversial. But a sudden relaxation of these measures without a vaccine or viable treatment for Covid-19 would allow the pandemic to continue spreading.

At the same time, the unprecedented resources flowing toward a vaccine doesn’t mean it will arrive any sooner. Even in the best of times, developing a vaccine is an enormous technical challenge that pushes the frontiers of science, demands the focus of swarms of researchers, and requires grueling trial and error. Despite the dozens of candidates under review, there is no guarantee any of them will pan out.

And those candidates that do show promise then need to undergo extensive testing for safety. A Covid-19 vaccine would have to be administered to millions, if not billions, of people. That means the rate of complications from the drug has to be so low that giving it to so many people is still a net positive.

For instance, one concern with vaccines is the risk of a problem known as vaccine enhancement or immune enhancement. That’s where the recipient’s immune system overreacts to the vaccine and may worsen the disease. It’s rare, but the likelihood of it has to be reduced as much as possible and balanced against the efficacy of a vaccine.

Still, a vaccine that offers imperfect protection could still be distributed; a vaccine that hasn’t met minimum safety thresholds could not.

In contrast, a treatment is only administered to people who are already ill, or as a preventive measure to people who face a high likelihood of getting infected. The risks and side effects for a treatment are more tolerable because they are weighed relative to the damage from the virus.

Reaching the point where a vaccine is ready to deploy requires extensive, slow, tedious, and expensive testing in humans. Until a vaccine reaches the necessary safety benchmarks, its use will be delayed. That’s a big reason pharmaceutical companies have been reluctant to invest in vaccine development on their own. But this testing is also why vaccines are some of the safest medical tools ever developed.

Some vaccines could be used before testing is completed under compassionate use guidelines, or for people in high-risk roles. A research team at Oxford University’s Jenner Institute said they may have a vaccine ready for emergency use as soon as September. However, a widespread rollout will take much longer.

Distribution: Will countries compete or collaborate on a global vaccination campaign?

The next obstacle to ending the Covid-19 pandemic with a vaccine is getting to enough people inoculated to achieve herd immunity. That’s where enough members of a population are immune to the virus, making it so that the virus can’t spread easily. The herd immunity threshold in a population can range from 60 percent to more than 90 percent, depending on how readily the pathogen can spread. At those levels, even people who aren’t immune receive protection since the virus is less likely to jump from person to person.

Depending on the prevalence of the virus at the time, that could mean vaccinating the majority of people on Earth. It’s not clear that the world will muster the resources, knowledge, and political will to do this.

“People don’t realize the full extent, that we as a country, we as a global community, have never vaccinated adult populations in the numbers that we need” to end the Covid-19 pandemic, said Saad Omer, a vaccine researcher and director of the Yale Institute for Global Health. “The numbers you would need for normalization — numbers you would need for NFL games to resume with crowds, the numbers you would need for a sense of normalcy, where grandma-can-attend-your-wedding kind of normalcy — would require vaccine-level herd immunity, and that would mean pretty high numbers.”

Billions of doses will be needed, which demands a robust supply chain and manufacturing capacity. Very little of this infrastructure exists now, and building it up would require extensive government and private sector investment.

A related issue is that different types of vaccines — mRNA, viral fragments, inactivated viruses — require entirely different manufacturing techniques, so one assembly line can’t be easily repurposed for another. Each approach requires its own infrastructure.

Vaccinating everyone would also demand legions of workers trained to administer it all over the world. It’s a process that will take years of sustained effort, and planning needs to begin right away. “Just the logistics for it are pretty substantial,” Omer said. “My concern is that we’re not preparing for it now.”

And at the outset, there won’t be enough vaccines for everyone, which means making difficult decisions about whom to prioritize for immunization.

Whether there will be enough vaccines to go around will depend on decisions and investments being made now. Philanthropists like Bill Gates, economists, and some nonprofits are calling to start building vaccine factories for different candidates immediately, even before testing is complete, with the expectation that many of these vaccine candidates will not be selected.

But a pandemic requires also international coordination. While researchers are sharing data about Covid-19 across borders, it’s not clear that countries agree on how to collaborate on making and distributing the vaccine. The US, for instance, has tried to lure vaccine developers to the country to make vaccines for exclusive US use. But the World Health Organization has called for sharing vaccine intellectual property free among companies and countries. Other world leaders have called for a people’s vaccine to Covid-19 to be made available to all countries free of charge.

The extent of global collaboration can therefore shape how quickly the pandemic phases out. If only a handful of countries have a Covid-19 vaccine and aren’t willing to help distribute it, the virus can continue to spread in other areas of the world. And until there’s herd immunity, the virus could be reimported into countries, even with a vaccine.

Public health responses: Can we keep up pandemic control measures until, and after, a vaccine arrives?

Since a Covid-19 vaccination campaign will likely take a long time, many of the current tactics to slow the pandemic will still be needed to an extent after a vaccine is available.

“Without a vaccine, it’s not as though we can do nothing,” said Meagan Fitzpatrick, an assistant professor at the center for vaccine development and global health at the University of Maryland School of Medicine. “With or without a vaccine, what we really need to be doing in the short term is contact tracing and testing. We need to test, trace, isolate.”

And limiting the spread of the virus can boost the effectiveness of a vaccine across a population, even if the vaccine itself doesn’t grant robust, long-term immunity to an individual. For instance, a vaccine that protects older people, coupled with social distancing and mask-wearing, would do more to slow the pandemic than any of these methods on their own. So a vaccine is ultimately one tactic in a suite of methods to control Covid-19.

“If the [moderately efficacious] vaccine is used outside of these comprehensive public health responses — contact tracing, social distancing — it would only protect the individual person for one to two years,” said Neuman.

Another element that could influence a Covid-19 vaccination campaign is the availability and effectiveness of treatments for the virus. Right now, there is no specific treatment recommended for general use — some experimental drugs like remdesivir have been allowed for emergency and compassionate use. However, if a widely available medicine were developed, it would relieve some of the urgency for developing a vaccine.

Treatments could also help optimize the distribution of vaccines. If a treatment is more effective in some groups but not others, say, the elderly, the more vulnerable group could become the priority for vaccination, putting limited vaccines to more effective use.

However, one of the biggest problems for Covid-19 vaccination may be the small but potent movement opposing vaccines. Already, some groups are whipping up conspiracy theories about purported harms of a vaccine that hasn’t even been developed yet. But if such resistance builds, it could undermine the effort to roll out a vaccine, allowing the virus to infect more people.

In thinking about how a Covid-19 vaccine would play out, it helps to look at lessons from other vaccines

The Covid-19 pandemic is unprecedented in many ways, so whatever scenario emerges will be unlike anything we’ve seen before. That said, there are some historical cases that can illustrate what could happen with a Covid-19 vaccine.

The most ideal outcome would be a vaccine akin to that for smallpox, rendering robust and near-lifelong immunity to the virus. With the smallpox vaccine, smallpox has become only one of two viruses to have been eradicated in the wild. “It’s obvious that we’re all aiming for a vaccine that is more like the smallpox vaccine,” Fitzpatrick said.

However, the world was very lucky with smallpox. The vaccine was unusually effective. The virus also had no known animal hosts and only spread from human to human.

Polio, another virus with an effective vaccine, lingers in some parts of the world despite an aggressive vaccination campaign, which has been thwarted by conflict and distrust of the vaccine. Now the Covid-19 pandemic is undermining some of the fragile progress against the disease.

That said, researchers do expect that a usable Covid-19 vaccine will emerge from the race. “I do have a lot of optimism about our ability to develop a vaccine against the coronavirus,” said Fitzpatrick. “The reason they are being tested now is because they have shown promising results in animal models.”

Even if a vaccine doesn’t prevent the disease entirely, it can still be useful if it reduces the severity of the illness. “You could imagine a scenario where something that is less than efficacious is rolled out because some benefit in the pandemic is better than no benefit,” said Omer. That would make it particularly helpful for people in high-risk groups like the elderly or people with preexisting health conditions.

But the lower levels of protection could also mean that an inoculated patient could still spread the virus, which means other control measures would be needed to protect high-risk groups.

On the other end of the spectrum, the race to develop a Covid-19 vaccine could be as fruitless as the effort to develop a vaccine for HIV, which has gone on for nearly 40 years.

Such an outcome would require weighing the trade-offs that may be necessary to live in a world where SARS-CoV-2 may be lurking for years. “We have to start thinking about prevention where we don’t have the magic bullet or the technological fix,” said Gregg Gonsalves, an assistant professor of epidemiology at the Yale School of Public Health.

For HIV, the lack of a vaccine to date has led public health officials to focus on treatments like antiviral drugs and to encourage less risky behavior, like using condoms. These tactics have improved the survival rate for people with the virus and reduced its spread. Similar attention to treatment and behavior could mitigate the harms of Covid-19, but it may require lasting cultural changes like wearing masks and avoiding large gatherings.

Researchers do expect that some versions of vaccines will start being deployed in the next few months in limited cases, but getting a widespread vaccine at a record pace would require a lot of the aforementioned factors to precisely fall into place. A vaccine could still arrive in time to be used to protect the majority of people. But the world will still have to endure the pandemic until then.

Even with assembly lines in place ready to ramp up production, there will likely be a scarcity of vaccines at the outset. That will require officials to ration the vaccine and make difficult decisions about whom to prioritize in their distribution.

“It’s not an easy decision to make, and I don’t envy the people who have to make it,” Durbin said.

The central focus of the vaccination campaign would be the people facing the most exposure to the virus, like health workers, followed by people in essential roles like those in grocery supply chains and first responders. Then older people and those at the highest risk of complications could be vaccinated.

One method to economize vaccines is a ring vaccination strategy. For Covid-19, it would involve vaccinating just people who were exposed to the virus rather than everyone in a population, forming a “ring” around a known carrier. Ring vaccination was used effectively in the Democratic Republic of Congo to contain the Ebola virus outbreak there in 2019. But it requires extensive contact tracing to figure out who might have been exposed. With a virus that spreads as far and as quickly as Covid-19, this tracing effort would be far more laborious than it was for Ebola, especially given that many people infected with SARS-CoV-2 can spread it without showing symptoms.

“We would definitely aiming for a [vaccine] supply where we didn’t have to consider ring vaccination as a strategy,” Fitzpatrick said.

Another scenario is that the distribution of the vaccine may take longer than the duration of immunity it provides. If a Covid-19 vaccine provides two years of protection but takes five years to reach most people, then the first round of immunity could fade before herd immunity is reached. That’s why it’s important to get the vaccine delivered quickly to as many people as possible. Otherwise, pockets of infection could remain and cause sporadic outbreaks until people are revaccinated.

Supply chains are critical too. If countries are willing to pool resources to ramp up vaccine production, the demand for a vaccine could be met far more rapidly than with countries working on their own. It would also prevent some of the bottlenecks that have hampered other materials needed for the Covid-19 pandemic, like personal protective equipment and reagents for tests.

Communication is also going to be a critical factor for the deployment of a vaccine to explain why vaccines are safe and why getting vaccinated is so important.

It’s a hard-learned lesson from other disease control efforts. Measles, for instance, surged in recent years as vaccination rates stagnated or declined in some areas, leading to 140,000 deaths worldwide in 2018. Part of this was due to a lack of investment in vaccination campaigns, but the outbreak also arose in insular communities with low vaccination rates, as well as among people deliberately avoiding the vaccine and denying its safety.

Even amid a deadly pandemic, it’s unlikely that people who fear vaccines will suddenly change their minds with Covid-19. “That’s not how it works. People have huge motivated reasoning,” Omer said. “There will be vaccine acceptance issues.”

Resolving this will require campaigns to convince people to get vaccinated aimed not necessarily at the people who are most opposed to vaccines, but at people who are ambivalent. Without this kind of outreach, even the existence of a highly effective vaccine won’t contain the virus.

Taken together, these scenarios highlight just how difficult it is to anticipate the pandemic’s future. But they also show why it’s important to game out what’s possible, to build for the best, and to prepare for the worst. Billions of lives and livelihoods worldwide hang in the balance.

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