A Big Unknown in Covid-19 Vaccine Development: How Long Will Protection Last?
Early trials suggest vaccines can induce antibody production, but it is too early to know how long they will work
If any of the most-advanced Covid-19 vaccines prove to work safely, they may protect people for months or years rather than the rest of their lives, according to emerging science and health experts.
Only a handful of vaccines generate lifetime immunity for most people, such as the ones for measles, a viral infection that naturally produces lifelong immunity. Experts caution against expectations of such longevity for Covid-19, citing experience with other respiratory viruses plus emerging data on the longevity of the antibodies that can prevent the virus from entering human cells and replicating.
To fill in knowledge gaps on vaccine duration, researchers and vaccine developers are looking closely at emerging science of immune responses in recovered patients, and how that science can be applied to vaccine development. They are also looking at previous coronaviruses and harnessing vaccine technologies that have worked against other viruses.
“Unfortunately, the questions of duration and immunity do take time to uncover,” said Philip Dormitzer, viral vaccine R&D chief for Pfizer Inc., which is developing a vaccine candidate with partner BioNTech SE.
Vaccine-makers usually learn how long a shot protects during a second-phase study in hundreds of patients that may require months or years to complete. However, to save time for Covid-19 vaccines, trial phases are being compressed or combined, so less is known about durability near the end of the testing process than normal.
The first Covid-19 vaccine study is expected to be completed in the fall, but scientists don’t have the luxury to wait until the science is settled, or at least better understood. An emergency authorization by regulators could come before duration is known. Trials are progressing as natural-immunity studies are rapidly pouring in from labs onto online servers and the pages of scientific journals.
Francis Collins, director of the National Institutes of Health, said it would be hard to know whether a Covid-19 vaccine protects for a year after testing it for only a few months, but he said recovered patients who don’t become reinfected after a year “would be a good sign that the vaccine ought to work” for at least that long.
A growing number of studies suggest most patients mount a robust immune response, including producing antibodies or other molecular defenses, to fight the virus after infection. One preliminary study from Mount Sinai in New York of nearly 20,000 people with suspected or confirmed Covid-19 found most had moderate or high levels of antibodies.
These findings are mirrored by preliminary results of experimental vaccines developed by Moderna Inc., MRNA -2.81% Pfizer Inc. and Oxford University that produced an immune response, which experts said is encouraging for the viability of vaccine candidates.
What remains unclear is how long natural defenses last and whether they protect people against reinfections—information that can be applied to understanding vaccine duration.
“For me, it’s the most important question in the field,” said Lynda Stuart, deputy director of vaccine development at the Bill & Melinda Gates Foundation.
Other early research suggests antibodies against SARS-CoV-2, the coronavirus that causes Covid-19, decline in some patients roughly two to three months after the onset of symptoms. A preliminary study of 65 patients posted online by U.K. scientists this month found that neutralizing antibodies, those that would prevent the virus from entering cells and replicating, declined over a 94-day period in experiments.
In a small study, Moderna’s vaccine increased neutralizing antibodies, especially during the two weeks after the second dose. But by four weeks after the second dose, those antibody levels had declined somewhat, though they were still elevated compared with the start of the study.
When the Mount Sinai researchers called back roughly 120 participants three months after they first got sick, most had antibodies, though they had waned a bit.
“That’s not unexpected,” noted Ania Wajnberg, an associate professor of internal medicine at Mount Sinai and lead author of the study. “Your body doesn’t need as many antibodies when it’s not sick anymore.”
That antibodies remain suggests even mild disease could induce a strong antibody response, raising hopes that a vaccine would be able to do the same, she said. Most patients in the study weren’t hospitalized and had mild to moderate Covid-19.
Moderna Chief Medical Officer Tal Zaks said it is too early to make any conclusions about durability based on the first study. Still, he said some of the company’s other experimental mRNA-based vaccines for other diseases have induced immune responses that last for months, though some decline over time.
Data doesn’t yet exist on whether antibodies or T-cells, which recognize and eliminate infected cells, will be more important for long-term protection against Covid-19, experts said. In a study published in the journal Nature this month, researchers found that patients who recovered from SARS and Covid-19 had T-cells that could recognize a SARS-CoV-2 protein.
Candidates from Pfizer, Moderna and Oxford all have shown some level of T-cell response.
Both Moderna and Pfizer are tracking volunteers to see how long immunity responses last. Their vaccines are slated to begin separate 30,000-person trials this month.
Oxford researchers said that the duration of its potential vaccine is currently unknown, but it is conducting studies to learn more about how long protection might last.
Experts also say Covid-19 vaccines may be easier to develop because SARS-CoV-2 appears to mutate less frequently than influenza, another RNA-based respiratory virus whose seasonal shifts have made an effective vaccine for the broad population elusive.
Some vaccines in development rely on technology that successfully boosted antibodies for other diseases for at least a year.
A candidate under development by Merck MRK -1.23% & Co. and nonprofit International AIDS Vaccine Initiative uses the same technology as its Ebola vaccine, which has shown in studies to provide protection from Ebola and generate antibodies that are maintained for at least three years. Human testing is expected to start later this year, said Nick Kartsonis, who oversees vaccine clinical research at Merck.
Johnson & Johnson’s JNJ -1.00% candidate, expected to start human testing this month, is using the same technology as its experimental shot against the Zika virus, which was able to generate elevated antibody levels for more than a year.
How well any vaccine stacks up against one another is a critical question, given the varying risk among some populations, experts said.
“It’s important to do a head-to-head trial…That to me is the biggest thing I want to know and am concerned about,” said Stanley Perlman, a University of Iowa coronavirus researcher. “We don’t know which part of the immune response will be induced best by each of these vaccines.”