Department of Physiology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Laboratory of Creative Science for Insect Industries, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 819-0395, Japan.
Int J Mol Sci. 2024 Sep 26;25(19):10379. doi: 10.3390/ijms251910379.
During the COVID-19 pandemic, diabetic and obese patients experienced higher rates of hospital admissions, severe illness, and mortality. However, vaccinations failed to provide those vulnerable populations the same level of protection against COVID-19 severity as those without diabetic and obese phenotypes. Our study aimed to investigate how diabetes mellitus (DM) impacts the immune response following vaccination including the artificially designed trimeric SARS-CoV-2 spike (S)-protein. By using two diabetic mouse models, ob/ob mice (obese, hyperglycemic, and insulin-resistant) and STZ-treated mice (insulin-deficient and hyperglycemic), we observed a significant reduction in S-protein-specific IgG antibody titer post-vaccination in both diabetic models compared to wild-type (WT) mice. Both diabetic mouse models exhibited significant abnormalities in spleen tissue, including marked reductions in splenic weight and the size of the white pulp regions. Furthermore, the splenic T-cell and B-cell zones were notably diminished, suggesting an underlying immune dysfunction that could contribute to impaired antibody production. Notably, vaccination with the S-protein, when paired with an optimal adjuvant, did not exacerbate diabetic cardiomyopathy, blood glucose levels, or liver function, providing reassurance about the vaccine's safety. These findings offer valuable insights into potential mechanisms responsible for the decreased persistence of antibody production in diabetic patients.
在 COVID-19 大流行期间，糖尿病和肥胖患者的住院率、重症和死亡率较高。然而，疫苗未能为这些易感染人群提供与非糖尿病和肥胖表型人群相同水平的 COVID-19 严重程度保护。我们的研究旨在调查糖尿病（DM）如何影响接种疫苗后的免疫反应，包括人工设计的三聚体 SARS-CoV-2 刺突（S）-蛋白。通过使用两种糖尿病小鼠模型，ob/ob 小鼠（肥胖、高血糖和胰岛素抵抗）和 STZ 处理的小鼠（胰岛素缺乏和高血糖），我们观察到与野生型（WT）小鼠相比，这两种糖尿病模型在接种疫苗后 S-蛋白特异性 IgG 抗体滴度显著降低。两种糖尿病小鼠模型的脾脏组织均表现出明显异常，包括脾脏重量和白髓区域显著减小。此外，脾 T 细胞和 B 细胞区明显减少，表明存在潜在的免疫功能障碍，可能导致抗体产生受损。值得注意的是，S-蛋白与最佳佐剂联合接种并未加重糖尿病心肌病、血糖水平或肝功能异常，这为疫苗的安全性提供了保证。这些发现为糖尿病患者抗体产生持久性降低的潜在机制提供了有价值的见解。
