Insulin deficiency inhibits 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 diabetes-related factors underlying this impaired immunity remain unclear, but defining them is critical for improving vaccine strategies in this vulnerable population. Here, we isolated insulin deficiency as a contributing factor to decreased vaccine-mediated immune responses using a mouse model. Following immunization with an alum-adjuvanted protein subunit vaccine, insulin-deficient mice exhibited reduced antigen-specific IgG antibody responses, decreased B-cell and T-cell 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 further revealed significantly smaller germinal center volumes in insulin-deficient mice compared with 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 in this process. This work establishes a framework for defining the mechanisms of diabetes-related immune suppression and guiding the design of more effective vaccines tailored to the unique immunological requirements of people with diabetes.