交叉展示
抗原
细胞毒性T细胞
信使核糖核酸
抗原呈递
细胞生物学
病毒学
T细胞
生物
免疫系统
免疫学
体外
遗传学
基因
作者
Gokulnath Mahalingam,Hari Krishnareddy Rachamalla,Porkizhi Arjunan,Karthik V. Karuppusamy,Yogapriya Periyasami,Aruna Mohan,Kanimozhi Subramaniyam,Mohammad Salma,Vigneshwar Rajendran,Mahesh Moorthy,George Varghese,Mohankumar Murugesan,Saravanabhavan Thangavel,Alok Srivastava,Srujan Marepally
标识
DOI:10.1016/j.ymthe.2024.02.028
摘要
Abstract
The continual emergence of SARS-CoV-2 variants has necessitated the development of broad cross-reactive vaccines. Recent findings suggest that enhanced antigen presentation could lead to cross-reactive humoral responses against the emerging variants. Towards enhancing the antigen presentation to dendritic cells (DCs), we developed a novel shikimoylated mannose receptor targeting lipid nanoparticle system (SMART-LNPs) that could effectively deliver mRNAs into DCs. To improve the translation of mRNA, we developed spike domain-based trimeric-S1 (TS1) mRNA with optimized codon sequence, base modification, and engineered 5'&3' UTRs. In a mouse model, SMART-LNPs-TS1 vaccine could elicit robust broad cross-reactive IgGs against Omicron sub-variants, and induced IFNγ producing T-cells against SARS-CoV-2 virus compared to non-targeted LNPs-TS1 vaccine. Further, T-cells analysis revealed that SMART-LNPs-TS1 vaccine induced long-lived memory T-cell subsets, Th1-dominant and cytotoxic T-cells immune responses against SARS-CoV-2 virus. Importantly, SMART-LNPs-TS1 vaccine produced strong Th1-predominant humoral and cellular immune responses. Overall, SMART-LNPs can be explored for precise antigenic mRNA delivery and robust immune responses. This platform technology can be explored further as a next-gen delivery system for mRNA-based immune therapies.
科研通智能强力驱动
Strongly Powered by AbleSci AI