A new study in monkeys suggests that a blood test could predict the effectiveness of a Covid-19 vaccine — and perhaps speed up the clinical trials needed to get a working vaccine to billions of people around the world.
The study, published on Friday in Nature, reveals telltale blood markers that predict whether a monkey’s immune system is prepared to wipe out incoming coronaviruses.
The finding raises hope that researchers will be able to look for the same markers in people who get vaccines in clinical trials. If the markers are strong enough, they could reveal if the vaccines protect against Covid-19. And researchers would no longer have to wait for some trial volunteers to get the disease, as they do now.
“It will pave the way for a much more rapid advancement of the Covid vaccine field,” said Dr. Dan Barouch, a vaccine expert at Beth Israel Deaconess Medical Center in Boston and one of the researchers behind the new study.
Last month brought the stunning news that clinical trials of two new coronavirus vaccines, one from Moderna and the other from Pfizer and BioNTech, showed efficacy rates around 95 percent.
The strength of these two vaccines is, paradoxically, bad news for the dozens of others in earlier stages of development. Many of them will most likely have to be compared against the robust front-runners rather than a placebo shot. Because that is a high statistical bar to clear, their trials will need a lot more volunteers, time and money.
“You’d have to follow millions of people for a long time,” said Dr. Nelson Michael, the director of the Center for Infectious Diseases Research at Walter Reed Army Institute of Research, where a protein-based vaccine is being prepared for clinical trials in early 2021. “It’s just fantasy.”
For some smaller companies, these comparison trials may be deal-breakers. “You’re going to see a lot of dropout,” said Dr. Gregory Poland, a vaccine expert at the Mayo Clinic.
That’s a big problem, because Pfizer and Moderna won’t have nearly enough doses to give to everyone in the United States, let alone the world. And the next wave of vaccines may turn out to be superior to the first, in one way or the other. They could cost a lot less, for example. Some might come in just one dose instead of two, and won’t need a deep freeze. Some might offer protection that lasts a lot longer.
“We’d rather not have to revaccinate the world every one or two years,” Dr. Michael said.
The new monkey study offers a ray of hope for these next-generation vaccines, suggesting that they could be tested not against older vaccines, but using a measurement known as a “correlate of protection.”
“That’s the holy grail of vaccine research,” Dr. Michael said.
Influenza vaccines are already tested this way. Every new flu season requires the design of a new flu shot, but researchers don’t have to run clinical trials comparing it with old versions. Instead, they just check whether the new vaccine triggers a person’s immune system to make enough of a certain kind of antibody against the flu. If it does, then researchers know the vaccine is adequately stimulating the immune system.
If scientists could discover a correlate of protection against the coronavirus, they could follow the example of the flu. “That is an entirely plausible and feasible scenario,” said Dr. Anthony Fauci, the director of the National Institutes of Allergy and Infectious Diseases.
A spokeswoman for the Food and Drug Administration said that basing clinical trials on correlates of protection — if they turn out to exist — “possibly could be considered in the future.”
In their new study, Dr. Barouch and his colleagues found a correlate of protection in monkeys. They built the experiment on their previous research showing that once monkeys recover from Covid-19, they can resist a second infection. The scientists drew blood from these exposed animals and isolated an array of protective antibodies called IgG.
As the coronavirus vaccine get closer to U.S. authorization, here are some questions you may be wondering about:
- If I live in the U.S., when can I get the vaccine? While the exact order of vaccine recipients may vary by state, most will likely put medical workers and residents of long-term care facilities first. If you want to understand how this decision is getting made, this article will help.
- When can I return to normal life after being vaccinated? Life will return to normal only when society as a whole gains enough protection against the coronavirus. Once countries authorize a vaccine, they’ll only be able to vaccinate a few percent of their citizens at most in the first couple months. The unvaccinated majority will still remain vulnerable to getting infected. A growing number of coronavirus vaccines are showing robust protection against becoming sick. But it’s also possible for people to spread the virus without even knowing they’re infected because they experience only mild symptoms or none at all. Scientists don’t yet know if the vaccines also block the transmission of the coronavirus. So for the time being, even vaccinated people will need to wear masks, avoid indoor crowds, and so on. Once enough people get vaccinated, it will become very difficult for the coronavirus to find vulnerable people to infect. Depending on how quickly we as a society achieve that goal, life might start approaching something like normal by the fall 2021.
- If I’ve been vaccinated, do I still need to wear a mask? Yes, but not forever. The two vaccines that will potentially get authorized this month clearly protect people from getting sick with Covid-19. But the clinical trials that delivered these results were not designed to determine whether vaccinated people could still spread the coronavirus without developing symptoms. That remains a possibility. We know that people who are naturally infected by the coronavirus can spread it while they’re not experiencing any cough or other symptoms. Researchers will be intensely studying this question as the vaccines roll out. In the meantime, even vaccinated people will need to think of themselves as possible spreaders.
- Will it hurt? What are the side effects? The Pfizer and BioNTech vaccine is delivered as a shot in the arm, like other typical vaccines. The injection won’t be any different from ones you’ve gotten before. Tens of thousands of people have already received the vaccines, and none of them have reported any serious health problems. But some of them have felt short-lived discomfort, including aches and flu-like symptoms that typically last a day. It’s possible that people may need to plan to take a day off work or school after the second shot. While these experiences aren’t pleasant, they are a good sign: they are the result of your own immune system encountering the vaccine and mounting a potent response that will provide long-lasting immunity.
- Will mRNA vaccines change my genes? No. The vaccines from Moderna and Pfizer use a genetic molecule to prime the immune system. That molecule, known as mRNA, is eventually destroyed by the body. The mRNA is packaged in an oily bubble that can fuse to a cell, allowing the molecule to slip in. The cell uses the mRNA to make proteins from the coronavirus, which can stimulate the immune system. At any moment, each of our cells may contain hundreds of thousands of mRNA molecules, which they produce in order to make proteins of their own. Once those proteins are made, our cells then shred the mRNA with special enzymes. The mRNA molecules our cells make can only survive a matter of minutes. The mRNA in vaccines is engineered to withstand the cell’s enzymes a bit longer, so that the cells can make extra virus proteins and prompt a stronger immune response. But the mRNA can only last for a few days at most before they are destroyed.
The researchers set out to see if there was a level of IgG that reliably protected monkeys from Covid-19. If the IgG antibodies produced by vaccines were above that level, the vaccines could be judged effective.
To find that line, the researchers gave monkeys varying doses of antibodies, and then exposed them all to the coronavirus and watched how well they fought off the infection. In the monkeys with the weakest dose, the viruses multiplied much as they would in an ordinary animal.
But the monkeys that got a medium dose produced far fewer viruses. Some of them were able to wipe out the viruses altogether. At the highest dose, the monkeys were completely protected.
Until now, scientists relied on circumstantial evidence that suggested IgG antibodies were crucial to clearing coronavirus infections. The new study puts that idea to the test — and determines the threshold of IgG antibodies required to ward off an infection.
“This is the first time, to the best of my knowledge, that we’ve actually proven that antibodies protect,” Dr. Barouch said. “Everything else has been a statistical association.”
The experiment revealed that a modest amount of IgG antibodies turned out to be enough. That could be heartening news for vaccine developers, because even so-so vaccines may be able to cross the threshold.
Researchers are now starting to review the results of vaccine clinical trials to see if a correlate of protection like the one identified by Dr. Barouch and his colleagues in monkeys exists in people. “The study bodes well for the upcoming immune correlates studies,” said Holly Janes, a biostatistician at the Fred Hutchinson Cancer Institute in Seattle who was not involved in Dr. Barouch’s study.
Although it will take some time for those studies to produce solid results, Dr. Janes said preliminary hints made her optimistic.
“The emerging data do suggest that we could be gleefully surprised,” she said.
Rebecca Robbins contributed reporting.