The first COVID-19 vaccine likely won’t be effective enough to end the global pandemic, vaccine experts say. Instead, we may live with the virus for years before a winning one emerges.
In July, the first large-scale human trial of two coronavirus vaccine candidates will start, according to US health officials, who are sounding increasingly confident that some kind of vaccine will be ready to be distributed widely by December.
“I'm cautiously optimistic that with the multiple candidates that we have with different platforms that we're gonna have a vaccine,” said National Institute of Allergy and Infectious Diseases chief Anthony Fauci, speaking on Tuesday at a briefing held by the Journal of the American Medical Association (JAMA). He predicted that nearly 100 million doses of a successful vaccine would be available by November or December, and perhaps 200 million doses by the beginning of 2021, largely due to taxpayer and philanthropic investments in factories that will be built to manufacture the massive quantity of vaccines.
The White House’s Operation Warp Speed is expected to name five companies — Moderna, AstraZeneca, Johnson & Johnson, Merck, and Pfizer — to lead the vaccine effort in the US, according to the New York Times.
Vaccines essentially imitate an infection — without getting you sick — training your immune system to quickly produce antibodies to repel a real attack. The biggest hope for a vaccine came after a May study showed that nearly everyone who recovers from COVID-19 produces antibodies to the coronavirus, also called SARS-CoV-2, meaning that the virus can be fought with vaccination. “That's a pretty good proof of concept to say that you're going to make an immune response in response to a vaccine,” said Fauci.
But what makes a successful vaccine? The first ones to emerge from the 10 candidates now being tested in people worldwide are likely to resemble the seasonal flu shot. These vaccines need to be administered year after year and are sometimes only around 30% effective at blocking an infection, while at the same time promising milder symptoms to people who do get sick. That’s in stark contrast to other vaccines, like the one for measles, where two shots confer immunity for a lifetime.
“When people talk about the race for the COVID-19 vaccine, I have to say, ‘Be careful what you wish for,’” said vaccinologist Peter Hotez of the Baylor College of Medicine. “History tells us that the first ones have a built-in obsolescence.”
Here’s what our vaccine future might look like:
There are four types of coronavirus vaccines in progress — some promising and others hyped.
Along with the 10 SARS-CoV-2 vaccines now in human trials, more than 120 others are under study in test tubes and lab animals, according to the World Health Organization. Each one aims to, hopefully, produce enough of the right “neutralizing” antibodies to prevent future infections. The trials take two groups of study volunteers, randomly picked to either get a real vaccine or a placebo, and then measure for differences in how many people get infected or have severe symptoms.
Broadly speaking, the candidates work by four methods, only two of which have long been proven to work in past vaccines. The first is to give people a weakened or killed form of an actual virus, used in polio, chicken pox, and flu vaccines. The second proven way is to just inject a small fragment of the virus to trigger immune readiness, like the HPV vaccine or newer flu vaccines.
A third cutting-edge approach is under study by AstraZeneca and the University of Oxford, whose vaccine is expected to enter a large human trial in July. It works by taking a chimpanzee virus and coating it with the tiny spikes that cover the surface of SARS-CoV-2. The chimp virus causes a harmless infection in humans, but the spike proteins will prime the immune system to recognize signs of a future SARS-CoV-2 invasion.
That's in theory. “There isn't a guarantee ever that you're going to get an effective vaccine,” said Fauci. The US Biomedical Advanced Research and Development Authority has provided more than $1 billion for the Oxford vaccine’s development, and AstraZeneca has announced a plan to test the candidate in more than 10,000 people in the United Kingdom. But in early data, the vaccine has underwhelmed observers, who noted it didn’t prevent infections in monkeys, just lessened their symptoms. William Haseltine, a former Harvard Medical School professor known for pivotal research on cancer and HIV, noted the neutralizing antibodies produced by the vaccines were “extremely low,” in Forbes.
“Time will tell if this is the best approach,” Haseltine concluded. “I wouldn’t bet on it.”
The fourth approach is a genetic vaccine, where only the genes that cells need to produce the coronavirus spike are injected into a person. Those spike proteins, dutifully produced by cells in response to the genes, alarm the immune system and should produce immunity.
One genetic vaccine that’s emerged as a Wall Street favorite is being developed by a company called Moderna. Expected to begin large-scale human trials by July under Operation Warp Speed, the company has dismayed scientists by only releasing press releases with sparse data on its small safety experiments in people, feeding hype about its vaccine candidate.
The only vaccine that has published strong results — albeit only in monkeys and other lab animals — is from China’s Sinovac biotech firm, which relied on the old-fashioned method of injecting a small amount of dead viruses to prime the immune system against a real infection. “That’s an old-school vaccine,” said Hotez. “We do know those work.”
Without the full data measuring the effects of the vaccines in people, however, outside experts tend to be skeptical of their ability to prevent an infection. Vaccine experts prefer candidates to be at least 70% effective at preventing infections, Paul Offit of Children’s Hospital of Philadelphia said at a separate JAMA briefing on Monday. Still, even if the vaccine only lessens the severity of a deadly disease, he added, that “would be great, because it keeps you out of the hospital, it keeps you from dying.”
But scientists warn we should expect delays — especially if the pandemic continues to die down.
The two Operation Warp Speed candidates will begin human trials in 30,000 people in the first week of July, Fauci said. In these trials, happening largely in the US but also overseas, some volunteers will randomly receive an inoculation and others will receive a placebo. These studies are at the mercy of the size of the outbreak where they take place, because you need enough people in the placebo group to become infected to know the vaccine is working.
If the trial locations don’t have a high rate of infections, “it could take months and months and months to get an answer,” said Fauci. On the other hand, if the trials take place amid a big surge in cases, “you could get your answer pretty quickly.”
With infections continuing but not spiking nationwide, likely due to people continuing to follow physical distancing measures, there’s a real concern that the clinical trials could stretch out for months. If this happens, typically trials have to add more participants, causing delays. A 2006 rotavirus vaccine trial in 40,000 children grew to more than 70,0000 for that reason, said Offit, and stretched out for more than three years. “It's hard to study something that doesn't happen.”
That might easily delay a vaccine past December. Ken Frazier, the CEO of Merck, one of the firms reportedly selected for the Warp Speed trials, told the Financial Times in May that the 12- to 18-month timeline the program called for was “very aggressive” and set an unrealistic standard for his company.
Whatever vaccines do emerge might not make us immune for a lifetime.
Even when researchers have an answer, Offit added that he would be surprised if a SARS-CoV-2 vaccine is ever much more than 70% effective at stopping infections. That’s because of the short incubation time that respiratory illnesses, like the flu or COVID-19, give even a prepared immune system to ramp up defenses and release antibodies. It takes four to five days for people exposed to the coronavirus to begin to develop symptoms. In contrast, measles has an incubation time of 10 to 12 days, part of what makes the measles vaccine 97% effective for a lifetime after just two doses.
Fauci also worries that people will need somewhat frequent coronavirus vaccine booster shots, noting that immune system antibodies tend to wane after an infection with the four everyday coronaviruses that cause around 20% of common colds. Hotez was less concerned about this, arguing the immune system should still retain a memory of spike proteins, through other immune cells that can last in the body for decades. But he acknowledged that it still needs to be studied, given that SARS-CoV-2 has only been known to scientists for six months.
“We're going to have to manage expectations,” said Offit. Vaccinating 20,000 people in a clinical trial is not the same as vaccinating 200 million people. Rare side effects may only emerge after those millions of people take the vaccine, he said. The duration of immunity will probably only be revealed after the vaccines are widely used.
The expectation is that healthcare workers, older people in nursing homes, and others most at risk for infection would be first in line for vaccines, Fauci told BuzzFeed News in February.
The way the coronavirus vaccines will roll out might resemble the history of the polio vaccine, where new generations of inoculations were steadily released over decades. In another historical similarity, the March of Dimes paid five firms to mass-produce the first Salk polio vaccine in 1954, before it was even proven effective in April 1955, after field trials involving more than 1.8 million children. The 1955 polio vaccine was judged 80% to 90% effective, while today three doses are 99% to 100% effective.
Other scientists are concerned about what will happen when the vaccine is rolled out.
Another concern is about who is seen as leading the US vaccine effort. The CDC, which typically manages the country’s vaccine programs, has taken a backseat in the response to the pandemic — and has stayed largely silent on the subject of a coronavirus vaccine. The secrecy surrounding Operation Warp Speed plays into the hands of an anti-vaccination movement premised on conspiracy theories about doctors, the government, and pharmaceutical firms, said Hotez.
It’s a real worry: In a May poll, less than half of Americans said they would take a COVID-19 vaccine, with 20% saying they would reject one altogether.
“It should be the CDC managing the vaccine rollout, with the nation's public health agencies in every state,” said Hotez.
Typically vaccines undergo a 10-month review process from the FDA, or a shorter 6-month one for “expedited” reviews. But because the vaccine is urgently needed, it may be rushed out even more quickly — making some experts concerned we could end up prioritizing speed over finding the best vaccine possible. The FDA has already drawn scrutiny for emergency authorizations for experimental drugs of uncertain benefit, blood tests with low accuracy, and a CDC diagnostic test that didn’t work for most states.
A final vaccine worry is whether as the November election approaches, the Trump administration might spring a vaccine that hasn’t completed its clinical trial on the public as an “October surprise,” said Offit. The result could be a permanent disaster for public confidence in vaccines, especially if the FDA goes along with such a move under pressure from the White House, as some are arguing the agency did with the malaria drugs used to treat COVID-19. “That would be a tragedy,” he said.
“I think there's every reason that vaccines are going to be the hero of this story,” said Offit. “But we have to attend to the science, and we have to be humble.”