Research News

Researchers from Cleveland Clinic’s Florida Research & Innovation Center (FRIC) have reported higher levels of exhausted and immature memory B cells in people who do not receive protection from influenza vaccines. Their Frontiers in Immunology study aims to improve flu vaccine effectiveness through understanding differences in immune response. 

“Vaccines are not just medical tools; they are a cornerstone of public health, with far-reaching benefits,” says study first author, Laise Rodrigues Reis, PhD. “This information gives immunologists and manufacturers information they need to improve the flu vaccine’s effectiveness, potentially save lives and enhance quality of life for everyone.” 

How does the flu vaccine work with memory B cells? 

Vaccines use small, safe pieces of a virus called antigens to train the memory B cells in our immune systems to recognize invaders. Memory B cells never forget this training. The cells can quickly recognize the real virus based on its antigen and call for backup from the immune system to generate antibodies, even years after the shot (long-term immunity).   

Dr. Reis theorized if immunized individuals with low immune response to the virus had differences in their memory B cells compared to people with high immune activity. 

“Despite widespread vaccination efforts, a subset of individuals fails to mount a protective immune response. They can be susceptible to infection and its complications,” Dr. Reis says. “Understanding the differences in the immune response to influenza vaccination can support vaccine strategies to aimed at preventing outbreaks and protecting at-risk and susceptible groups.” 

How do differences in memory B cells influence vaccine effectiveness? 

When the memory B cells don’t work properly pathogens can sneak past our immune system’s first line of defense undetected. That can make us sick, even if we were vaccinated.  

In collaboration with investigators from the University of Georgia and René Rachou Institute-FIOCRUZ in Belo Horizonte, Brazil, Dr. Reis performed long-term memory B cell analyses of 21 individuals who received annual flu vaccines between 2019 and 2024. Half of the individuals had robust immune responses (measured by serological tests), while the other half were non-responders. Together, the team found that non-responders had a high level of exhausted, abnormal, memory B cells. This may suggest a deficiency in replication, maturation and generation of antibodies in response to the influenza virus.  

What do we need to do before we can activate memory B cells to improve how the flu vaccine works? 

In an ideal scenario, strategies to modulate exhausted and immature memory B cells could enhance vaccine efficacy and promote a more robust and durable immune response, Dr. Reis explains. Other Cleveland Clinic laboratories are studying memory B cells for similar reasons. For example, the laboratory of Giuseppe Sautto, PhD, recently published a paper in the Journal of Immunology characterizing the antibody responses of different memory B cells. 

On a larger scale, Dr. Reis is excited to test whether exhausted and immature memory B cells influence how we respond to other vaccines and pathogens. 

“While my early research focused on Yellow Fever, my focus has always been on the underlying immunological principles that govern vaccine responses, regardless of the specific disease,” she says. “That is how I was able to seamlessly transition into studying influenza, and how I hope to transition into assessing the B-cell responses to other pathogens or vaccines.”