{"doi":"10.1101/2025.09.24.677144","title":"Insulin-deficient diabetes impairs vaccine-mediated antibody and germinal center B-cell formation in mice","abstract":"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.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":575964,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9517,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":337399,"name":"Pablo Ariel","orcid":"0000-0002-8494-0379","position":1,"is_corresponding":false},{"id":275061,"name":"Mark T. Heise","orcid":"0000-0001-5829-8477","position":2,"is_corresponding":false},{"id":425637,"name":"Lance R. Thurlow","orcid":"0000-0003-1839-2922","position":3,"is_corresponding":false},{"id":676437,"name":"Christopher J. Genito","orcid":"0000-0002-9044-964X","position":0,"is_corresponding":true}],"reference_count":33,"raw_metadata":null,"created_at":"2026-07-19T02:57:52.712371Z","pmid":"41040392","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}