Six Questions About Waning Immunity to Covid-19 Answered

When Pfizer, Moderna and Johnson & Johnson announced their Phase 3 clinical trial results, suggesting that their injections were 95 percent, 95 percent and 67 percent effective at preventing infection, respectively, experts cheered. All three vaccines provided what seemed to be nearly impenetrable walls against severe COVID-19 disease. However, as the pandemic has worn on and reports of breakthrough infections made national headlines, the FDA and CDC recommended a shot to boost immunity among all adults six to eight months after their second shot of Pfizer or Moderna’s vaccine, or two months after the first shot of Johnson & Johnson.

Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases recently told the New York Times that immunity is “waning to the point where you’re seeing more and more people getting breakthrough infections, and more and more of those people who are getting breakthrough infections are winding up in the hospital… boosters will be an essential part of the protection.”

Experts say “waning immunity” is concerning, but it isn’t as scary as it sounds. The vaccines still work, and for most people, still provide a high level of protection against severe disease. “It’s been a challenge,” says Mark Slifka, an immunologist at Oregon Health and Science University. “because some people will say, ‘well the vaccines aren’t working.’ And that’s a misconception. Vaccines are still providing 90 percent protection against mortality and hospitalization.” Breakthrough infections have increased but infections are still three times more likely in unvaccinated than vaccinated individuals. Of those infections, only 3.9 percent have led to hospitalization in vaccinated patients compared to 9 percent in those who remain unvaccinated.

New variants also play a role in waning immunity. Mutations like those seen in the new Omicron variant may help the virus sneak past our immune system, but scientists don’t yet know if this is the case for Omicron.

To learn more about waning immunity and how to protect against it, we reached out to the experts.

1. What happens when you get the COVID-19 vaccine?

Your immune system has three main soldiers that work together to recognize and stop infections from wreaking havoc on your body: antibodies, B cells and T cells.

We’ve been hearing about antibodies since the beginning of the pandemic, and for good reason. These proteins are one of the most important components of immunity and they’ve also been used in both testing and treatment for COVID-19. They’re created by B cells.

Vaccination spurs B cells to churn out the SARS-CoV-2-specific antibodies that fill your blood after infection or vaccination and attach to different parts of the virus. Neutralizing antibodies are your best defense. They cling to the spike protein on the outside of the virus which stops it from entering your cells, effectively neutralizing the danger.

“Antibodies are fantastic. They take care of a lot of viruses that are floating around in your body,” says Richard Kennedy, a vaccine expert at the Mayo Clinic. “But once the virus gets inside a cell, antibodies can't do anything about it. So that's where your T cells come in.”

Vaccination also stimulates the production of T cells. Instead of recognizing the virus alone, like an antibody, T cells find and kill your own cells after they’ve been infected, so the virus can’t spread. “The T cells are not that great in preventing an infection but absolutely crucial for terminating an infection,” says Alessandro Sette, an infectious disease and vaccine researcher at the La Jolla Institute for Immunology. “If you have a good T cell response, you’ll have less severe disease.”

2. What does waning immunity look like?

After an infection or vaccination, your body keeps building up its immune army in case the invader is still lurking in your veins. Your B cells keep secreting—and even improving—antibodies specific to the virus for some time. But when they don’t come in contact with the enemy for an extended period of time, they slow down production and the cells and proteins gradually die off causing your immunity to start to wane. “Imagine the B cells and the T cells as soldiers that are there fighting an infection and antibodies are bullets that are shot by B cells,” says Sette. “It doesn't make sense for the immune system to continue to fire bullets if an invader is gone.” 

After your antibody levels fall, a small percentage of B and T cells will stick around as “memory cells,” which can live for months, years and sometimes even decades. If the virus (or a booster shot) returns, these cells can rapidly ramp up your immune response. But if they don’t see the virus again, even they eventually start to die and your immunity will wane further.

How long the cells stick around depends on what virus they’re trained to kill. “The measles, mumps and rubella (MMR) vaccine can give many years of protection. Then you have the flu vaccine, which at most can give you a couple months of protection,” says Slifka. Other vaccines, like the Pertussis vaccine land somewhere in the middle, with protection plummeting several years after vaccination—with the CDC recommending a booster be administered later in life. While SARS-CoV-2 antibodies start to wane after a few months, scientists don’t yet know how long memory B and T cells stick around.

3. What does waning immunity look like with COVID-19 vaccines?

About six to eight months after your second jab of Pfizer or Moderna or two months after your first of Johnson & Johnson, your antibody levels start to fall, and scientists have found your likelihood of getting a breakthrough infection rises, though you’re still mostly protected from severe disease and death. This is the start of waning immunity.

“We’re seeing a lot of breakthrough cases,” says Rosemary Rochford, an immunologist at the University of Colorado, Anschultz School of Medicine. “But we don’t see as much breakthrough disease.” Those with breakthrough infections are still far less likely to end up in the hospital than those who are unvaccinated.

Immunity is not an on-off switch, explains Kennedy. “It’s very much a spectrum.” If you have a very high level of antibodies, they’ll wipe out the virus before an infection can take hold and you won’t experience any symptoms. If your antibodies wane a little, it may take a bit longer for your immune system to wipe the virus out, but the disease will be relatively short and mild. At some point, if you have few or no immune cells left, you’ll have little or no immunity left and you’ll be as vulnerable to infection as you were before your body was ever introduced to the virus.

“Initially, we saw antibodies declining, but protection was [still] high,” says Slifka. Now, “protection against severe disease is also waning, but not as quickly.”

4. Can an antibody test tell me if I need a booster shot?

Not yet. There are two main reasons for this. First, scientists haven’t identified the exact level of antibodies you need to be protected, called an immune correlate of protection. To do this, they’d need to have access to blood samples taken from a vaccinated population almost immediately before an outbreak. Then, they can evaluate the number of antibodies in each blood sample and compare that to who got sick and how sick, while assuming that their exposure to disease was about the same.

It’s taken some serendipity to discover this threshold for some other diseases. For example, finding this number for measles was a sort of convenient accident, explains Slifka. A measles outbreak in a mostly vaccinated population happened at Boston University in 1985, immediately after a blood drive. Using samples from the donated blood, researchers could compare the level of antibodies leftover from vaccination in each sample with who got sick and who didn’t and find the level at which individuals lost protection.

The other reason scientists don’t know when each individual needs booster shots is that antibody levels only tell part of the story. In their absence, T cells can take over. “If you have a lot of antibodies, you don't need any of those other immune functions. You don't need any T cells,” says Kennedy. However, “if you don't have a lot of antibodies, but you do have a lot of T cells, then [the T cells] can compensate.” That means that even if you had a very low level of antibodies, you could still be protected.

5. What role do new variants play?

As the virus mutates, it’s possible that the changes allow it to evade our immune system’s recognition. This is why there’s a new influenza vaccine every year—the virus mutates so quickly that the previous year’s shot doesn’t provide adequate protection the next year.

Several new variants of SARS-CoV-2 have emerged—and some, like Delta and Omicron, have mutations in the spike protein that might help them avoid antibody detection—but none have been completely able to elude vaccine-induced immunity yet.

However, the Delta variant is far more infectious than previous variants, meaning that a person with this strain usually carries far more viruses than someone infected with another strain. Instead of hiding from the immune system, in some cases it can overwhelm it with massive numbers. “If you have one virus get inside a body with 100 antibodies, piece of cake, you can wrap it up and you won’t get infected.” Says Rochford. “Now, if you have 1000 viruses get in and you've got 100 antibodies, you can overwhelm [the antibodies] and it takes a little bit longer [for the antibodies to overcome the virus] so you can establish that infection.”

Scientists are running experiments now to see how the vaccines fare against Omicron. It’s not yet known whether the mutations in its spike protein help it evade immunity, or affect the transmission or severity of disease.

Since a booster shot can increase your level of antibodies, it can help protect against the Delta variant. Additionally, when scientists took blood samples from individuals after their first and second doses of the Pfizer vaccines, they found that after the second shot, antibodies were able to neutralize more strains of the virus. “The booster dose not only increases the magnitude of the antibody response, but also increases the breadth to different variants that aren't even in the formulation,” says Slifka.

T cells formed after infection or vaccination mount robust immune responses against the Delta variant, according to a September 2021 correspondence in Nature. The authors of the predict that patients whose antibodies don’t neutralize the Delta variant will experience mild breakthrough infections, but “if the T cells are still there, it's likely that they will still be able to prevent severe disease,” says Sette.

6. So when should I get my third shot?

Everyone’s immunity wanes at different rates, so the CDC and FDA have had to identify the time that seems to make the most sense for most individuals. “You don’t want to tell everybody you have to get a booster every month. That would definitely provide a lot of protection but now you’re over-vaccinating people,” says Kennedy. Breakthrough infections seem to become more common around six to eight months after two doses of Pfizer or Moderna, which is why that’s the recommended timeline. If you have a compromised immune system, you should consider getting a third shoot earlier, suggests Kennedy, but for most individuals, anywhere in the six-to-eight-month range would be practical for those with the mRNA vaccines. Regulators recommend a second shot two months after receiving the first Johnson and Johnson vaccine.

Kennedy adds that in addition to the rate at which your immunity wanes, you should consider your risk of exposure. Ask yourself what you’ll be doing over the next few months. If your plans include traveling or large gatherings like sporting events and family get-togethers, you might consider getting your booster shot sooner rather than later.

To Rochford, the answer to when to get a booster is simpler. “When you can,” she says.