For those who have delayed getting vaccinated because they have already been infected with the coronavirus, a growing body of evidence suggests that vaccination combined with natural immunity provides particularly strong protection, including against virus variants.

So-called hybrid immunity, which combines natural immunity from infection with vaccine immunity, appears to provide better protection than infection or vaccination alone.

“There is a really dramatic increase in immunity in people who have previously been infected if they get at least one dose of vaccine,” said Shane Crotty, an immunology professor at the La Jolla Institute for Immunology in California. “Against some of the most concerning variants, the levels of antibodies after vaccination are literally 100 times higher than before for someone with natural immunity,” Crotty said. “That is not a minor adjustment.”

Oregon Health and Science University’s Fikadu Tafesse, an assistant professor of molecular microbiology and immunology, agreed. Tafesse’s study discovered that vaccination increased levels of neutralizing antibodies against variant forms of the coronavirus in people who had previously been infected.

“You will get better protection if you get vaccinated as well as an infection,” he said. Though having had a previous case of Covid-19 provides some immunity, the amount of protection varies, leaving some people vulnerable to reinfection.

“Antibody levels are really variable after recovering from infections, and those at the lower end of the spectrum may be more vulnerable to reinfections,” said Deepta Bhattacharya, an immunology professor at the University of Arizona. “However, after a single vaccine, antibodies skyrocket in people who have recovered from Covid-19, including those that neutralize concern variants.”

Researchers at Rockefeller University in New York City examined how different types of immunity would protect against potential variants in a study published on the preprint server BioRxiv. (Studies available on preprint servers have not been peer-reviewed.) In order to do so, they created a modified version of the coronavirus spike protein with 20 naturally occurring mutations to see how antibodies would react to it.

In lab dishes, these modified spike proteins were tested against antibodies from people who had recovered from Covid-19, those who had been vaccinated, and those who had hybrid immunity. The spike proteins were able to avoid detection by antibodies from the first two groups, but not by antibodies from people with hybrid immunity.

Another study, conducted by researchers at the Centers for Disease Control and Prevention, discovered that among those who had previously been infected, vaccination reduced the risk of reinfection by more than twofold when compared to natural infection alone.

According to Crotty, the immunological advantage of hybrid immunity stems in part from what are known as memory B cells, which are immune cells that produce antibodies to fight off viruses.

“Memory B cells are basically antibody factories that have had the lights turned off,” Crotty explained. “If the virus gets past your first line of defense, which is circulating antibodies, memory B cells can activate and produce more antibodies.”

After being exposed to a threat, these cells are trained to produce antibodies against that threat, such as the coronavirus. Memory B cells, on the other hand, don’t just make antibodies that have worked in previous infections; these cells are constantly tinkering with the formula, producing antibodies that could target variants of viruses that don’t yet exist.

Both vaccine-induced immunity and natural infection activate the antibody-generating abilities of memory B cells. However, research has found that memory B cell levels are higher in people with hybrid immunity than in people who only have natural infection or vaccination.

This could explain why people with hybrid immunity have a broader range of antibodies.

Crotty explained that the antibodies “recognize all these things that other people just don’t recognize.”

This recognition may extend beyond the virus variants that cause Covid-19: According to a study published in the journal Science in June, hybrid immunity antibodies can recognize the original SARS virus from 2003. Crotty is encouraged by the findings, which suggest that a vaccine against all coronaviruses could be developed in the future.

“You could have a vaccine that recognizes a wide range of current and future coronaviruses, which is not a pipe dream,” he said. “The data support that is truly possible.”