How COVID-19 Immunity Works at This Point in the Pandemic

When SARS-CoV-2 was a brand-new virus, it met little resistance in immune-naïve hosts—that is, us.

Vaccines, boosters, and infections have increased our immunity to varying degrees. But how much protection do each of these provide at this point in the pandemic? Here’s what researchers are learning about how the human body reacts to COVID-19 and its vaccines and boosters.

Vaccines generate more antibodies than infections

When the immune system meets a new intruder like SARS-CoV-2, its first response is to churn out sticky antibody proteins that attach to the virus and block it from binding to and infecting cells. Viruses can’t reproduce on their own and need to co-opt other cells to make more copies of themselves—so the fewer viruses that can infect cells, the fewer viruses that can circulate in a person’s body and make that person sick.

Immunization is the most effective way to launch this antibody production against SARS-CoV-2. Getting infected with the virus itself also triggers the process, but to a lesser extent. Studies show that levels of antibodies against the COVID-19 virus are higher among people who are vaccinated than among those who are unvaccinated and get infected.

However those antibodies are produced, they tend to wane after a few months. Still, that doesn’t mean the immune system has checked out of the fight.

Antibodies keep evolving

Just as SARS-CoV-2 evolves and mutates to evade immune defenses, antibodies also get better at seeking out and disabling viruses. They accomplish this in several ways. First, they get stickier in order to more tightly bind to the virus. When the immune system first encounters a virus, it might take a dozen or so antibodies to sufficiently neutralize it—but it could take just a single evolved antibody to accomplish the same feat. “With repeated doses [of vaccine], it looks like the antibodies do improve qualitatively, and not just quantitatively,” says Dr. Otto Yang, professor of medicine at the University of California, Los Angeles. “They become more efficient.” The same is true of antibodies generated by infections, but researchers can track antibody evolution better with each successive dose of a COVID-19 shot, since it’s not always obvious when people get infected.

Secondly, over time, antibodies branch out and target different parts of the virus as an insurance policy against mutations the virus is generating. “The immune system is also relearning,” says Ugur Sahin, co-founder of BioNTech (the company that, with Pfizer, developed one of the COVID-19 mRNA vaccines). This process takes time, so the protection against new variants isn’t immediate.

But it does work. Dr. David Ho, director of the Aaron Diamond AIDS Research Center at Columbia University, recently reported that people vaccinated and boosted with the original mRNA vaccines generate similar levels of antibodies against some of the newer Omicron variants as people who got the updated Omicron-specific booster. This phenomenon, called immune imprinting, may explain why people who were vaccinated with the original shots may have waning levels of antibodies that make them vulnerable to getting infected, but once they are infected, even with the latest variants, they don’t seem to develop severe COVID-19. This shows that the antibodies are apparently changing in response to the new viruses they are encountering.

T-cell immunity strengthens with time

After antibodies block as many viruses as they can from infecting cells, another population of immune cells kicks in. T cells are designed to recognize and remember viruses in order to shut down future infections more quickly. T cells keep tabs on known pathogens and arm cells that are able to kill and eliminate these intruders before they cause serious illness.

With each vaccination, booster dose, or infection, these T cells continue to proliferate. They not only recognize the specific virus they encounter, but, like the antibodies, are also flexible enough to evolve and target less mutated portions of SARS-CoV-2. That explains why people vaccinated with the original shots are still well protected from getting severely ill even if they are infected with newer Omicron strains.

A past infection doesn’t provide bullet-proof immunity

Past infections can also provide some protection, but it’s not long-lasting. Antibodies produced after an infection peak a few months after recovery, then start to wane (just like the initial wave of antibodies generated by vaccines). That’s why the U.S. Centers for Disease Control and Prevention recommend that people wait about three months after recovering from COVID-19 before getting a booster shot, since their immune systems are already stimulated and may react more aggressively with side effects to the shot.

In a recent study, Sahin and his team reported that people infected with early Omicron variants—such as BA.1, which first appeared in late 2021—were still vulnerable to getting infected with newer variants such as BA.4/5, which emerged in early 2022. But even if the antibodies can’t prevent infection, both the T-cell response and the evolution of the antibodies can protect against severe COVID-19.

COVID-19 immunity is complex—but vaccines and boosters are still key

Since so many people have been vaccinated, boosted, and infected, it’s hard to tell whether what component affords the greatest protection. And with SARS-CoV-2, immunity hasn’t worked the way immunologists have expected it to.

Usually, getting infected with any given virus produces broader immunity than getting vaccinated against it. That’s because when you’re infected, your immune system is exposed to the entire virus and can generate defenses against any parts of it. That response is typically more layered than the limited one provoked by vaccines.

However, studies of people vaccinated against COVID-19 do not bear that out. “When we compare vaccinated people vs. those who had one less vaccine and then a breakthrough infection, people with the breakthrough infection should be better protected against another infection, but they are not,” says Sahin. “The data show that adding one vaccine dose provides better protection than adding an infection.”

The reason for that isn’t entirely clear, but it may be related to the fact that the virus is focused on bypassing the existing immune response so that it can continue to infect cells and spread to new hosts. Stimulating a strong immune response is not in the virus’ best interest, as that would make its primary goal of infecting more cells and making more copies of itself a challenge. Vaccines, on the other hand, are designed to jumpstart a robust immune response to ensure and put the immune system’s defenses on high alert.

However, neither past vaccination nor infection necessarily provides protection against later strains of this ever-evolving virus. In his latest paper, Sahin reported that people vaccinated with the Omicron booster targeting BA.4/5 showed strong levels of neutralizing antibodies against previous Omicron strains, but the same wasn’t true of people vaccinated with a BA.1 booster whose blood was then exposed to BA.4/5.

There’s another important difference between the protection provided by vaccines vs. natural infections. Getting COVID-19 comes with the risk of symptoms, including durable ones in the form of Long COVID. “The risk of natural infection for some infections, like SARS-CoV-2, still outweighs the potential immune benefits,” says Dr. Egon Ozer, director of the center for pathogen genomics and microbial evolution at the Havey Institute for Global Health at Northwestern University.

Will yearly updated COVID-19 boosters be necessary?

It’s clear that vaccinations and boosters will continue to play an important role in protecting against COVID-19. It will take time for the latest BA.4/5 boosters to generate the broadest range of immunity via antibodies and T cells, so public-health experts may need a few more months of data to decide whether people will need to get additional boosters, and if so, which ones.

The good news is that since Omicron emerged in late 2021, most of the variants have remained in the Omicron family—mutating in different ways from the main virus, but not enough to classify an entirely new branch of the SARS-CoV-2 tree.

For now, the combination of vaccines, boosters, and infections is building a type of immunity against SARS-CoV-2 that is keeping most people from needing hospital care or dying. However you generate that immunity, the good news is that the immune system “has got a little flexibility built in,” Ozer says. “Not every immune cell is completely identical to the other.”