Study shows that higher levels of memory B cells are associated with reduced risk of COVID-19 vaccine breakthrough infection

A study led by A*STAR’s Infectious Diseases Labs (A*STAR ID Labs) has identified an immune cell population—known as memory B cells—that is associated with a reduced risk of COVID-19 vaccine breakthrough. The study found that patients with higher levels of these cells are more resistant to a vaccine breakthrough.  

Like antibodies, memory B cells selectively act against a target. While antibodies act like front-line troops ready to defend the body against the pathogen target, memory B cells act as reserves, taking some time to activate and multiply upon encountering the pathogen. Afterwards, the resulting activated B cells secrete much more antibody, resulting in a stronger antibody response against the pathogen. Many vaccines in use today are able to induce memory B cells against their respective pathogen targets, but the importance of these cells in helping to protect against disease is not well understood.

The goal of the study was to understand whether a difference in memory B cells or any other arm of the immune system may have helped to protect close contacts of infected patients, specifically those who had been vaccinated but not infected. Researchers examined a cohort of over 50 patients who had been infected with the Delta strain of COVID-19 despite having been vaccinated, and compared them with a cohort of over 80 of the vaccinated close contacts of the infected individuals.  

Researchers tested various aspects of the immune response, including antibody levels, memory B cell levels and T cell levels. The study found that among these, memory B cell levels were lower in the vaccine breakthrough cases, although the levels of antibodies were similar in both groups.

These findings highlight the potential role of memory B cells to provide protection against Delta variant infection in vaccinated populations. Further research is ongoing whether they may demonstrate similar protective activity against Omicron and its subvariants.

Notably, it is generally thought that memory B cells last longer than antibodies, and therefore may contribute toward long-lived immunity after vaccination. Hence, it remains important for the general public to continue getting their vaccinations and booster shots, wherever necessary. Further research is ongoing to identify how long such potentially protective memory B cell responses may last, which may help predict the level of COVID-19 susceptibility in a population.

Dr Matthew Zirui Tay, Investigator in the Laboratory of Antimicrobial Biologics at A*STAR ID Labs, and co-first author of the study, said, “Memory B cells have been known to be able to recognise more diverse variants of a virus compared to the antibody response. That may help explain why the memory B cells protected against the Delta variant here, which is divergent from the vaccine strain.”

Dr Angeline Rouers, Senior Research Fellow in the Laboratory of Pathogen Immunobiology at A*STAR ID Labs, and co-first author of the study, said, “Our study highlights how analysing the immune response in-depth played a key role in identifying this previously under-appreciated cell population. This was only possible because of an ecosystem team effort that has been ongoing since the start of the pandemic.”  

Prof Lisa Ng, Executive Director of ID Labs and corresponding author of the study, said, “COVID-19 continues to be a global menace, and new variants continue to emerge unpredictably. Our study on memory B cells opens up a new avenue of exploration toward long-lasting next-generation vaccines that may be able to help protect against diverse variants.”

The National Centre for Infectious Diseases (NCID) provided the clinical samples for the study. Prof David Lye, Director of Infectious Disease Research and Training Office at NCID, and corresponding author of the study said, “Understanding the immune response underpinning COVID-19 breakthrough infections in vaccinated patients may help in better design of future vaccines in preventing COVID-19 infections especially with new variants such as Delta and Omicron. To protect against future variants, it is important to get vaccinated and boosted.”

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