Smith Olivia A, Fujimoto Brent, Wong Teri Ann S, To Albert, Odo Troy, Ball Aquena, Haun Brien K, Muramatsu Hiromi, Tam Ying K, Pardi Norbert, Lehrer Axel T
Department of Tropical Medicine, Medical Microbiology, and Pharmacology, University of Hawaii Manoa, Honolulu, HI 96813, USA.
Cell and Molecular Biology Graduate Program, University of Hawaii Manoa, Honolulu, HI 96813, USA.
COVID. 2025 Jan;5(1). doi: 10.3390/covid5010002. Epub 2024 Dec 24.
The emergence of SARS-CoV-2 has resulted in a significant impact on public health, particularly for individuals with underlying health conditions such as obesity and diabetes. While vaccination efforts have played a crucial role in reducing hospitalizations, it remains unclear whether the effectiveness of these vaccines varies among different population groups. In this study, we investigated the immune responses generated by various SARS-CoV-2 vaccine platforms in mouse models with obesity and diabetes, focusing on both cell-mediated and humoral immune responses. Our findings revealed diminished immune responses in diabetic and obese mice compared to healthy counterparts. After vaccination with adjuvanted subunit or mRNA lipid nanoparticle (LNP) vaccines, both humoral and cell-mediated responses were significantly reduced in diabetic mice. Obese mice also exhibited decreased immunogenicity, albeit to a lesser extent. However, it should be noted that mRNA vaccines demonstrated strong neutralizing responses across all metabolic states, while adjuvanted subunit vaccines elicited higher antibody avidity in mice with type 2 diabetes (T2D) and obesity compared to healthy mice. These results suggest that the impaired humoral and cell-mediated responses observed in altered metabolic states may be linked to chronic inflammation associated with obesity and suboptimal glycemic control in diabetes. Understanding the impact of these metabolic disturbances on vaccine immunogenicity is crucial for developing optimized vaccines that can effectively enhance immune responses and provide long-lasting protection against SARS-CoV-2, even in individuals with obesity and diabetes. By contributing these findings, we support efforts to improve vaccine efficacy in populations affected by metabolic disorders, advancing effective immunization against SARS-CoV-2.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的出现对公众健康产生了重大影响，尤其是对患有肥胖症和糖尿病等基础健康问题的个体。虽然疫苗接种工作在减少住院率方面发挥了关键作用，但这些疫苗的有效性在不同人群中是否存在差异仍不清楚。在本研究中，我们调查了各种SARS-CoV-2疫苗平台在患有肥胖症和糖尿病的小鼠模型中产生的免疫反应，重点关注细胞介导免疫反应和体液免疫反应。我们的研究结果显示，与健康小鼠相比，糖尿病和肥胖小鼠的免疫反应有所减弱。在用佐剂亚单位疫苗或信使核糖核酸脂质纳米颗粒（LNP）疫苗接种后，糖尿病小鼠的体液免疫反应和细胞介导免疫反应均显著降低。肥胖小鼠的免疫原性也有所下降，尽管程度较轻。然而，应该指出的是，信使核糖核酸疫苗在所有代谢状态下均表现出强烈的中和反应，而与健康小鼠相比，佐剂亚单位疫苗在2型糖尿病（T2D）和肥胖小鼠中引发了更高的抗体亲和力。这些结果表明，在代谢状态改变时观察到的体液免疫反应和细胞介导免疫反应受损可能与肥胖相关的慢性炎症以及糖尿病中不理想的血糖控制有关。了解这些代谢紊乱对疫苗免疫原性的影响对于开发优化疫苗至关重要，这些疫苗能够有效增强免疫反应并为SARS-CoV-2提供持久保护，即使是对患有肥胖症和糖尿病的个体也是如此。通过提供这些研究结果，我们支持提高受代谢紊乱影响人群疫苗效力的努力，推动针对SARS-CoV-2的有效免疫接种。
