The idea of waning immunity has picked up steam in recent weeks, with some countries using it to justify rolling out third-dose COVID-19 vaccine boosters to their populations. But immunologists say the concept has been largely misunderstood.
While antibodies — proteins created after infection or vaccination that help prevent future invasions from the pathogen — do level off over time, experts say that’s supposed to happen.
And it doesn’t mean we’re not protected against COVID-19.
Jennifer Gommerman, an immunologist with the University of Toronto, said the term “waning immunity” has given people a false understanding of how the immune system works.
“Waning has this connotation that something’s wrong, and there isn’t,” she said. “It’s very normal for the immune system to mount a response where a ton of antibodies are made and lots of immune cells expand. And for the moment, that kind of takes over.
“But it has to contract, otherwise you wouldn’t have room for subsequent immune responses.”
Antibody levels ramp up in the “primary response” phase after vaccination or infection, “when your immune system is charged up and ready to attack,” said Steven Kerfoot, an associate professor of immunology at Western University in London, Ont.
Memory of pathogen remains
They then decrease from that “emergency phase,” he said. But the memory of the pathogen and the body’s ability to respond to it remain.
Kerfoot said B-cells, which make the antibodies, and T-cells, which limit the virus’s ability to cause serious damage, continue to work together to stave off severe disease long after a vaccine is administered. While T-cells can’t recognize the virus directly, they determine which cells are infected and kill them off quickly.
Recent studies have suggested the T-cell response is still robust several months following a COVID-19 vaccination.
“You might get a minor infection … [but] all of those cells are still there, which is why we’re still seeing very stable effectiveness when it comes to preventing severe disease,” Kerfoot said.
A pre-print study released this week by Public Health England suggested that protection against hospitalization and death remains much higher than protection against infection, even among older adults.
So the concept of waning immunity depends on whether you’re measuring protection against infection or against severe disease, Kerfoot said.
Ontario reported 43 hospitalized breakthrough cases among the fully vaccinated on Friday, compared with 256 unvaccinated hospitalized infections. There were 795 total new cases in the province that day, 582 among those who weren’t fully vaccinated or had an unknown vaccination status.
British Columbia, meanwhile, saw 53 fully vaccinated COVID-19 patients hospitalized over the last two weeks, compared with 318 unvaccinated patients.
“You’ll hear people say that vaccines aren’t designed to protect infection, they’re designed to prevent severe disease,” Kerfoot said. “I wouldn’t say necessarily it’s the vaccine that’s designed to do one or another … that’s just how the immune system works.”
Moderna, Pfizer back need for booster
Moderna released real-world data this week suggesting its vaccine was 96 per cent effective at preventing hospitalization, even amid the more transmissible delta variant, and 87 per cent effective at preventing infection — down from 94 per cent efficacy seen in clinical trials last year.
Moderna CEO Stéphane Bancel said that dip “illustrates the impact of waning immunity and supports the need for a booster to maintain high levels of protection.”
Pfizer-BioNTech has argued the same with its own data, and an advisory panel to the U.S.-based Food and Drug Administration voted Friday to endorse third doses for those aged 65 and older or at high risk for severe disease.
However, the panel rejected boosters for the general population, saying the pharmaceutical company had provided little safety data on extra jabs.
The University of Toronto’s Gommerman said the efficacy data presented by Moderna doesn’t signal the need for a third dose.
“The fact it protects 87 per cent against infection, that’s incredible,” she said. “Most vaccines can’t achieve that.”
Bancel said Moderna’s research, which has yet to be peer reviewed, suggested a booster dose could also extend the duration of the immune response by re-upping neutralizing antibody levels.
Looking beyond the antibody response
But Dr. Sumon Chakrabarti, an infectious physician in Mississauga, Ont., said looking solely at the antibody response is misleading and could be falsely used as justification for an infinite number of boosters.
Israel, which has opened third doses for its citizens, recently talked about administering fourth doses in the near future.
“This idea of waning immunity is being exploited, and it’s really concerning to see,” Chakrabarti said. “There’s this idea that antibodies mean immunity, and that’s true … but the background level of immunity, the durable T-cell stuff, hasn’t been stressed enough.”
While some experts maintain that boosters for the general population are premature, they agree some individuals would benefit from a third jab.
The National Advisory Committee on Immunization has recommended boosters for the immunocompromised, who don’t mount a robust immune response from a two-dose series.
Other experts have argued that residents of long-term care homes, who were prioritized when the rollout began last December, may also soon need a third dose. The English study suggests immunity could be waning in older groups but not much — if at all — among those under age 65.
Chakrabarti said a decrease in protection among older populations could be due more to “overlapping factors,” including their generally weaker immune systems and congregate-living situations for those in long-term care.
Immune cells live for years within bone marrow
“These are people at the highest risk of hospitalization,” he said. “Could [the length of time that’s passed following their doses] be playing a role? Yeah, maybe.”
While we still don’t know the duration of the immune response to COVID-19 vaccination, Gommerman said immune cells typically continue to live within bone marrow and make small amounts of antibodies for “decades.”
“And they can be quickly mobilized if they encounter a pathogen,” she said.
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