ALC-0315 Lipid-Based mRNA LNP Induces Stronger Cellular Immune Responses Postvaccination

Jan 15, 2025Molecular pharmaceutics

Lipid ALC-0315 in mRNA Vaccines May Boost Stronger Cell-Based Immune Responses

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Abstract

The ALC-0315-LNP vaccine elicited higher levels of IgG and activated immune cells compared to the MC3-LNP vaccine.

Both ALC-0315-LNP and MC3-LNP vaccines demonstrated high uniformity and stability.
Immunization with both vaccine formulations enhanced the formation and differentiation of germinal centers in mice.
Mice receiving the ALC-0315-LNP vaccine showed significantly greater activation of dendritic cells and T cells in draining lymph nodes.
Both LNP mRNA vaccines increased the activation of splenic T cells and Th1-type cytokine production.
The vaccines also significantly raised the proportions of follicular helper T cells and long-lasting plasma cells in draining lymph nodes on day 14 postimmunization.

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At the end of 2019, SARS-CoV-2 emerged and rapidly spread, having a profound negative impact on human health and socioeconomic conditions. In response to this unprecedented global health crisis, significant advancements were made in the mRNA vaccine technology. In this study, we have compared the difference between two SARS-CoV-2 receptor-binding domain (RBD) mRNA-Lipid nanoparticle (LNP) vaccines prepared from two different ionizable cationic lipids: ALC-0315 and MC3. Characterization of RBD mRNA-LNPs showed that both MC3-LNP and ALC-0315-LNP are highly uniform and stable. Furthermore, we assessed the humoral immune response in mice after immunization; our findings indicated that both vaccine formulations effectively enhanced the formation and differentiation of germinal center (GC). Notably, the mice immunized with the ALC-0315-LNP vaccine elicited higher levels of IgG and its subclasses and significantly enhanced the activation of dendritic cells and T cells in draining lymph nodes (dLNs) compared to those immunized with the MC3-LNP vaccine. Further analysis of the T cell phenotype after splenic restimulation showed that mice injected with both LNP mRNA vaccines had significantly increased activation of the splenic T cells and Th1-type cytokine production. In addition, our finding showed that both LNP mRNA vaccines significantly increased the proportions of follicular helper T cells (Tfh) and long-lasting plasma cells in the dLNs of mice on day 14 postimmunization compared to control. In conclusion, both ALC-0315 and MC3 exhibited good stability and immunogenicity as mRNA-LNP recipes, but the ALC-0315-based mRNA-LNP vaccine showed higher efficacy in humoral and cellular immune responses compared to MC3.

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ALC-0315 Lipid-Based mRNA LNP Induces Stronger Cellular Immune Responses Postvaccination

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