As more countries roll out booster doses of COVID-19 vaccines, conversations over how well these additional doses will protect people have centered on three things — breakthrough infections, waning antibody levels, and highly transmissible variants such as Delta and Omicron.

The production of antibodies is a key immune response to viruses, bacteria or other pathogens, but it’s not the body’s only way of fighting infection.
Booster doses are seen as a way to shore up the immune protection against SARS-CoV-2, the coronavirus that causes COVID-19.
More countries are rolling out boosters in the face of the Omicron variant, which can overcome some of the protection offered by vaccines.

All of these, of course, are interrelated.

The concern is that as antibody levels decline during the months after full vaccination, people will be less protected, especially from the highly contagious Delta and Omicron variants, which could increase breakthrough infections.

In addition, preliminary data suggests that Omicron may be able to overcome some of the immune protection offered by vaccines and prior infection.

Booster doses are seen as a way to shore up immune protection against SARS-CoV-2, the coronavirus that causes COVID-19.

However, the booster shot debate is more complicated than this.

When talking about how well COVID-19 vaccines work over time, there’s not only one type of effectiveness. Some vaccines might still prevent most people from getting severely ill or dying but may have less protection against infection that leads to minor symptoms.

In addition, antibodies are only one tool used by the immune system to fight infection. Focusing solely on antibody levels misses the protection offered by the other parts of the immune system, some of it longer-lived.

Still, it’s important to understand how antibodies work and what waning levels might mean for protection against COVID-19.

What are antibodies?

Antibodies are Y-shaped proteins the immune system produces in response to an infection. They recognize and bind to specific molecular structures — known as antigens — such as those found on the surface of a virus or bacterium.

Many of the antibodies involved in preventing coronavirus infection bind to the virus’s spike protein on the surface, which the virus uses to infect cells.

Antibodies are produced by immune cells called B cells, found in the blood, lymph nodes, spleen, and other tissues. Each B cell produces a specific type of antibody.

Scientists estimateTrusted Source that the human immune system can produce at least a trillion unique antibodies, although it could be substantially higher.

When the body encounters a virus or other pathogen for the first time, and a B cell can bind to that pathogen, the B cell is activated.

Once activated, a B cell multiplies and forms different cells, including plasma cells, which are antibody-producing factories.

Antibodies remain in the body for some time after infection, although their numbers wane over months or years, depending on the pathogen and other factors.

Adaptive and innate immune system: What to know

B cells and antibodies are part of the adaptive immune system, the branch that targets specific pathogens.

The other branch is known as the innate immune system, which provides a general defense against infection.

These two branches can work together to fend off a virus or bacterium before you get severely ill. If there is a virus or bacterium that your immune system has never encountered before, the innate immune response may sense something is wrong and respond quickly to an invading virus or bacterium.

This is important because it can take days to weeks for the adaptive immune system to effectively build up enough antibodies to fight the specific pathogen.

However, once your immune system has that exposure to the pathogen, it can then be ready to respond more quickly next time. Meaning it may be able to fend off invading bacterium or virus you’re exposed to before you develop any symptoms.

“If you’ve been exposed for the first time to a particular pathogen, and your adaptive immune system was involved, you will develop what are called memory cells — both on the T-cell side and the B-cell side,” explained Ralph Pantophlet, PhD, an associate professor at Simon Fraser University who studies antibody responses to HIV and other viruses.

One type of T cell, called helper T cells, stimulates B cells to produce antibodies. Another type, known as killer T cells, attacks cells that have already been infected by a pathogen.

“If you are re-exposed to the same pathogen or a very similar one, it’s usually the antibodies that help protect or blunt that second exposure,” said Pantophlet.

How vaccines work

Vaccines trigger a similar immune response without the risk of severe disease that comes with natural infection.

“[Vaccination] is basically a trick to provide the body with antibodies,” said Pantophlet, “so when you are exposed to ‘the real thing,’ you are protected, at least somewhat, from that assault.”

Vaccines accomplish this by presenting the immune system with an antigen from a pathogen.

Some vaccines contain the entire pathogen but in a weakened or inactivated form. Others contain only a specific piece of the pathogen.

The COVID-19 mRNA vaccines teach our cells how to make antibodies that target the coronavirus spike protein.

What antibody level is needed?

The immune system doesn’t produce only one antibody in response to a pathogen, but many different kinds. Some of these antibodies bind strongly to an antigen, others less so.

They can also be divided into neutralizing and non-neutralizing antibodies. As the name suggests, neutralizing antibodies can “neutralize” a pathogen.

For example, to respond to SARS-CoV-2, certain neutralizing antibodies bind tightly to the coronavirus spike protein and keep it from infecting the cell.

Although non-neutralizing antibodies don’t do this — or do it only weakly — they can still play a role in fighting pathogens.

“Non-neutralizing antibodies do not protect the cell from infection,” said Pantophlet. “However, non-neutralizing antibodies can recognize viral antigens that are exposed, or presented, on the surface of infected cells.”

When non-neutralizing antibodies bind to these surface antigens, other parts of the immune system can come along and eliminate the infected cells.

Pantophlet says that for COVID-19, most labs measure neutralizing antibodies “because that gives you a reasonable measure of protection [against infection].”

However, with COVID-19, he says we don’t yet have a clear sense of how high neutralizing antibody levels need to be to provide some protection from infection or severe disease.

Emily S. Barrett, PhD, an associate professor of biostatistics and epidemiology at the Rutgers School of Public Health, said identifying this minimum immune response is complicated because the immune system has other ways of protecting you besides antibodies. This includes the cellular, or T-cell-mediated, immune response.

“So, unfortunately, although we would all like to identify a threshold of protection, there’s no simple answer at the moment,” she said.

Still, “what we do know from just monitoring and measuring vaccine effectiveness,” said Pantophlet, “is that as the level of neutralizing antibodies decline, there is more chance of a breakthrough infection.”

In recent weeks, scientistsTrusted Source have inched closer to defining this protective immune response — or “correlate of protection” — for COVID-19, but we’re not quite there yet.

In the meantime, scientists rely on other measures to know how well vaccines are working. This includes looking at the effectiveness of vaccines in the real world, both in certain groups of people and over time.

This is the approach that Israel used in deciding to roll out COVID-19 boosters over the summer.

Data from the country showed that breakthrough infections were occurring more often in people who were vaccinated earlier in the year than those vaccinated more recently.

The lack of a correlate of protection for COVID-19 is also why you can’t take an antibody test — after vaccination or natural infection — to see how well protected you are against the coronavirus.

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