Study explains why vaccines underperform in people living with obesity

New findings reveal that obesity significantly impaired the quality and longevity of antibody responses to a Pseudomonas aeruginosa vaccine in a mouse model. The impaired antibody production was due to defects in germinal centers, a transient part of the immune system where specialized immune cells, called B cells, produce antibodies and build memory against pathogens

Researchers say the findings, which are published in The Journal of Immunology, provide an important reason for why traditional vaccines, which rely on high antibody production, tend to underperform in people with obesity.

We hope these findings shift the focus of vaccine design and lead to more effective, tailored vaccines for the millions of people living with obesity who are at higher risk for severe respiratory infections."

Wendy L. Picking, PhD, Professor, Department of Pathobiology and Integrative Biomedical Sciences, University of Missouri and lead author of the study

Though the antibody response was decreased, the vaccine did generate a strong response from lung tissue-resident memory T cells. These specialized cells live permanently in the lungs and do not circulate through the bloodstream. In response to the P. aeruginosa vaccine, resident memory T cells provided early, critical protection against infection that was not observed in mice fed a normal or low-fat diet. This suggests that the tissue-resident memory T cells could be compensating for antibody deficiencies.

"Instead of just trying to boost blood antibody levels, we should intentionally design vaccines that prioritize tissue-resident immunity, ensuring protection directly where pathogens like Pseudomonas enter the body," shared Dr. Picking.

P. aeruginosa is a leading cause of severe pneumonia for people with obesity and emerging antibiotic resistance increasingly makes the infection difficult to treat, highlighting the need for effective vaccines. To date, no other studies have examined the effectiveness of vaccines targeting gram-negative bacterial pathogens, like P. aeruginosa, in people with obesity. Understanding the relationship between obesity and the immune system addresses a significant gap in current vaccine research.

The researchers plan to build on these findings by identifying the specific molecular signals that enable the lung tissue-resident memory T cells to become activated despite the chronic inflammation associated with obesity. This could allow researchers to optimize vaccine formulations to further boost these resident memory cells. Ultimately, the researchers seek to create a vaccine that ensures robust protection for all individuals, regardless of their metabolic health.