Lymphoid Organs Remodeling in Non-Obese Diabetic Goto-Kakizaki Rats Immunized With SARS-CoV-2 Antigens

The COVID-19 pandemic revealed reduced vaccine efficacy and worse outcomes in people with type 2 diabetes mellitus (T2DM). However, how T2DM, independent of obesity, alters immune responses and lymphoid organ architecture remains unclear. We evaluated antibody production and lymphoid organ morphology following SARS-CoV-2 antigen immunization in Goto-Kakizaki (GK) rats, a non-obese T2DM model, to evaluate the isolated effect of diabetes. Ten-week-old male Wistar and GK rats received three intramuscular injections of SARS-CoV-2 antigens at 15-day intervals. Two antigen formulations were used: chemically inactivated whole SARS-CoV-2 containing aluminum hydroxide adjuvant and an inactivated Newcastle virus engineered to express the SARS-CoV-2 spike protein. Fifteen days after the final dose, anti-Spike IgG titers were measured by ELISA, and histological and morphometric analyses of lymphoid tissues were performed. GK rats exhibited elevated anti-Spike IgG responses compared with WT controls, regardless of the antigen formulation. Distinct morphological alterations in the lymphoid organs accompanied the enhanced IgG responses. Mesenteric lymph nodes from GK rats exhibited a morphology similar to that of WT rats. The thymus exhibited features of involution, including septal thickening, reduced corticomedullary distinction, diminished cortical cellularity, cortical thinning, and medullary expansion. The spleen showed white pulp remodeling, characterized by enlargement of germinal centers and periarteriolar lymphoid sheaths, along with a reduction in the marginal zone. We described herein the remodeling of the primary and secondary lymphoid organs in non-obese diabetic GK rats, which may play a role in the antibody response to an immune challenge.