Modeling immune suppression and decreased vaccine efficacy in diabetes: a role for insulin in germinal center B-cell and antibody responses to vaccination 2563

Description Individuals with diabetes mellitus have been shown to develop poorer immune responses and fewer protective antibodies in response to vaccination. This is concerning for the growing population of individuals with diabetes, projected to grow to 65 million people in the U.S. by 2050, who are at increased risk for serious infection from multiple vaccine-preventable diseases including influenza and COVID-19. The mechanism by which the immune response to vaccination is impacted by diabetes is largely unknown. Diabetes is characterized by the lack of insulin signaling, whether by insulin deficiency or insulin resistance. Insulin has been shown to play a role in the activation of multiple immune cell types, but less is known about its role in B-cells. We therefore aimed to evaluate the role of insulin in activating B-cells and generating antigen-specific antibodies to vaccines containing clinically relevant adjuvants. In response to vaccination in insulin-deficient mice, minimal antigen-specific antibodies were generated, and fewer germinal center B-cells were observed in the vaccine-draining lymph node. Light sheet microscopy revealed that average germinal center volume was smaller in insulin-deficient animals. These results demonstrate a role for insulin in the vaccine-induced immune response and sets up a model for improvement of vaccine strategies for the vast and rapidly growing population of individuals with diabetes. Funding Sources Supported by NIH NIAID R01AI173004 and UNC Chapel Hill Adams School of Dentistry Internal Funding. Topic Categories Vaccines and Immunotherapy (VAC)