Department of Biotechnology
inStem (Institute for Stem Cell Science and Regenerative Medicine)

SMART-lipid nanoparticles enabled mRNA vaccine elicits cross-reactive humoral responses against the omicron sub-variants.

Publication Type

Research Support, Non-U.S. Gov't

Date of Publication

May 1, 2024

Journal

Molecular therapy : the journal of the American Society of Gene Therapy

Volume/Issue

32/5

ISSN

1525-0024

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.

Alternate Journal

Mol Ther

PubMed ID

38414245

PubMed Central ID

PMC11081802

Authors

Gokulnath Mahalingam
Hari Krishnareddy Rachamalla
Porkizhi Arjunan
Karthik V Karuppusamy
Yogapriya Periyasami
Aruna Mohan
Kanimozhi Subramaniyam
Salma M
Vigneshwar Rajendran
Mahesh Moorthy
George M Varghese
Kumarasamypet M Mohankumar
Saravanabhavan Thangavel
Alok Srivastava
Srujan Marepally

Keywords

Humans
RNA, Messenger
Nanoparticles
T-Lymphocytes
Spike Glycoprotein, Coronavirus
Cross Reactions
SARS-CoV-2
Dendritic Cells
COVID-19
Immunity, Humoral
Antibodies, Viral
Animals
mRNA Vaccines
Lipids
Mice
Liposomes
Female
COVID-19 Vaccines