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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. Full article

Harnessing the immune system to combat disease has revolutionized medical treatment. Monoclonal antibodies (mAbs), in particular, have emerged as important immunotherapeutic agents with clinical relevance in treating a wide range of diseases, including allergies, autoimmune diseases, neurodegenerative disorders, cancer, and infectious diseases. These mAbs are developed from naturally occurring antibodies and target specific epitopes of single molecules, minimizing off-target effects. Antibodies can also be designed to target particular pathogens or modulate immune function by activating or suppressing certain pathways. Despite their benefit for patients, the production and administration of monoclonal antibody therapeutics are laborious, costly, and time-consuming. Administration often requires inpatient stays and repeated dosing to maintain therapeutic levels, limiting their use in underserved populations and developing countries. Researchers are developing alternate methods to deliver monoclonal antibodies, including synthetic nucleic acid-based delivery, to overcome these limitations. These methods allow for in vivo production of monoclonal antibodies, which would significantly reduce costs and simplify administration logistics. This review explores new methods for monoclonal antibody delivery, including synthetic nucleic acids, and their potential to increase the accessibility and utility of life-saving treatments for several diseases. Full article

RNA-based immunization strategies have emerged as promising alternatives to conventional vaccine approaches. A substantial body of published work demonstrates that RNA vaccines can elicit potent, protective immune responses against various pathogens. Consonant with its huge impact on public health, influenza virus is one of the best studied targets of RNA vaccine research. Currently licensed influenza vaccines show variable levels of protection against seasonal influenza virus strains but are inadequate against drifted and pandemic viruses. In recent years, several types of RNA vaccines demonstrated efficacy against influenza virus infections in preclinical models. Additionally, comparative studies demonstrated the superiority of some RNA vaccines over the currently used inactivated influenza virus vaccines in animal models. Based on these promising preclinical results, clinical trials have been initiated and should provide valuable information about the translatability of the impressive preclinical data to humans. This review briefly describes RNA-based vaccination strategies, summarizes published preclinical and clinical data, highlights the roadblocks that need to be overcome for clinical applications, discusses the landscape of industrial development, and shares the authors’ personal perspectives about the future of RNA-based influenza virus vaccines. Full article