Molecular therapy : the journal of the American Society of Gene TherapyFeb 28, 2024

Smart lipid nanoparticle mRNA vaccine triggers antibody responses against Omicron sub-variants

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗

Updated Mar 12, 2026

Abstract

The SMART-LNP-TS1 vaccine elicited robust broad cross-reactive IgGs against Omicron sub-variants in a mouse model.

Enhanced antigen presentation may lead to improved immune responses against emerging SARS-CoV-2 variants.
The novel shikimoylated mannose receptor targeting lipid nanoparticle system effectively delivered mRNAs into dendritic cells.
The vaccine induced interferon-γ-producing T cells against SARS-CoV-2 virus compared to a non-targeted version.
Analysis showed the vaccine generated long-lived memory T cell subsets, including T helper 1-dominant and cytotoxic T cells.
SMART-LNP-TS1 produced strong Th1-predominant humoral and cellular immune responses.

Simplified

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' and 3' 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 cells against SARS-CoV-2 virus compared with non-targeted LNP-TS1 vaccine. Further, T cells analysis revealed that SMART-LNP-TS1 vaccine induced long-lived memory T cell subsets, T helper 1 (Th1)-dominant and cytotoxic T 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.

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Declaration of interests The authors declare no competing interests.

PubMed

Smart lipid nanoparticle mRNA vaccine triggers antibody responses against Omicron sub-variants

Abstract

Full Text

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Competing interests

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Abstract

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