Insulin-deficient diabetes impairs vaccine-mediated antibody and germinal center B-cell formation in mice

Individuals with diabetes are at increased risk for severe outcomes from vaccine-preventable infections and often mount weaker immune responses to vaccination. The factors underlying this impaired immunity remain unclear, and defining them is critical to improve vaccine strategies for this vulnerable population. Here, we focused on insulin deficiency as a contributing factor. Following immunization with an alum-adjuvanted protein subunit vaccine, insulin-deficient mice exhibited reduced antigen-specific IgG antibody responses, decreased lymphocyte numbers, and lower germinal center B-cell counts within the vaccine-draining lymph node. Three-dimensional whole-organ light sheet microscopy combined with virtual reality-assisted analysis revealed significantly smaller germinal center volumes in insulin-deficient mice than controls. These findings indicate that insulin deficiency can significantly constrain germinal center responses and impair antibody production from vaccination. Our results provide foundational evidence that diabetes-associated metabolic changes can significantly and negatively influence the quality of vaccine-induced immunity and highlight insulin deficiency as a potential physiological factor.