@article {6593,
	title = {SMART-lipid nanoparticles enabled mRNA vaccine elicits cross-reactive humoral responses against the omicron sub-variants.},
	journal = {Mol Ther},
	year = {2024},
	month = {2024 Feb 27},
	abstract = {<p>The continual emergence of severe acute respiratory syndrome coronavirus 2 (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. Toward enhancing the antigen presentation to dendritic cells (DCs), we developed a novel shikimoylated mannose receptor targeting lipid nanoparticle (SMART-LNP) system 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{\textquoteright} and 3{\textquoteright} UTRs. In a mouse model, SMART-LNP-TS1 vaccine could elicit robust broad cross-reactive IgGs against Omicron sub-variants, and induced interferon-γ-producing T\&nbsp;cells against SARS-CoV-2 virus compared with non-targeted LNP-TS1 vaccine. Further, T\&nbsp;cells analysis revealed that SMART-LNP-TS1 vaccine induced long-lived memory T\&nbsp;cell subsets, T helper 1 (Th1)-dominant and cytotoxic T\&nbsp;cells immune responses against the SARS-CoV-2 virus. Importantly, SMART-LNP-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-generation delivery system for mRNA-based immune therapies.</p>
},
	issn = {1525-0024},
	doi = {10.1016/j.ymthe.2024.02.028},
	author = {Mahalingam, Gokulnath and Rachamalla, Hari Krishnareddy and Arjunan, Porkizhi and Karuppusamy, Karthik V and Periyasami, Yogapriya and Mohan, Aruna and Subramaniyam, Kanimozhi and M, Salma and Rajendran, Vigneshwar and Moorthy, Mahesh and Varghese, George M and Mohankumar, Kumarasamypet M and Thangavel, Saravanabhavan and Srivastava, Alok and Marepally, Srujan}
}
