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.

The speed at which several COVID-19 vaccines went from conception to receiving FDA and EMA approval for emergency use is an achievement unrivaled in the history of vaccine development. Mass vaccination efforts using the highly effective vaccines are currently underway to generate sufficient herd immunity and reduce transmission of the SARS-CoV-2 virus. Despite the most advanced vaccine technology, global recipient coverage, especially in resource-poor areas remains a challenge as genetic drift in naïve population pockets threatens overall vaccine efficacy. In this study, we described the production of insect-cell expressed SARS-CoV-2 spike protein ectodomain and examined its immunogenicity in mice. We demonstrated that, when formulated with CoVaccine HT™adjuvant, an oil-in-water nanoemulsion compatible with lyophilization, our vaccine candidates elicit a broad-spectrum IgG response, high neutralizing antibody titers, and a robust, antigen-specific IFN-γ secreting response from immune splenocytes in outbred mice. Our findings lay the foundation for the development of a dry-thermostabilized vaccine that is deployable without refrigeration.