Mind the Age Gap: Expanding the Age Window for mRNA Vaccine Testing in Mice DOI Creative Commons

Muattaz Hussain,

Agata Ferguson-Ugorenko,

Robert Macfarlane

et al.

Vaccines, Journal Year: 2025, Volume and Issue: 13(4), P. 370 - 370

Published: March 30, 2025

Background/Objectives: Murine models play a key role in guiding formulation and immunogenicity studies across various vaccine platforms, including mRNA-based vaccines. Typically, narrow age range (6 to 8 weeks) is used these studies. Here, we investigated whether widening this could provide greater flexibility experimental design without impacting pre-clinical outcomes. Methods: To achieve this, evaluated two commonly lipid nanoparticle (LNP) formulations (based on SM102 ALC-0315 ionizable lipids) containing either firefly luciferase or ovalbumin mRNA female BALB/c mice aged 4, 8, 16 weeks. LNPs were prepared purified via microfluidics, their size, polydispersity, zeta potential, encapsulation efficiency measured. Mice injected intramuscularly, the vivo bioluminescence antibody titers measured evaluate expression profiles three groups. Results: Our findings show that 4-week-old exhibited higher protein following administration compared older groups; however, no significant differences observed between 8- 16-week-old mice. Despite initial expression, responses after prime dose lower other However, booster dose, levels comparable all Conclusions: By identifying broader window, study design, enhance data comparability studies, promote more efficient use of animal resources, while maintaining reliable representative results murine models.

Language: Английский

Frit-Inlet Asymmetric Flow Field-Flow Fractionation for the Analysis of Lipid Nanoparticle-Protein Interactions DOI Creative Commons

Rand Abdulrahman,

Panida Punnabhum,

Robin Capomaccio

et al.

Journal of Chromatography A, Journal Year: 2025, Volume and Issue: 1743, P. 465663 - 465663

Published: Jan. 11, 2025

Research into nanoparticle interactions with biomolecules has become increasingly important in nanomedicine. While lipid nanoparticles (LNPs) are widely used as drug delivery systems, there remains a gap understanding their fate circulation, which is crucial for selecting appropriate lipids during formulation development. This study the first to use Asymmetric Flow Field Fractionation (AF4) compare two types of LNPs: MC3-LNPs and SM-102-LNPs, model protein, bovine serum albumin (BSA). AF4 offers high-resolution separation, ability simultaneously perform multiparametric inline analysis multiple detectors. In this study, impact LNP size, morphology PDI on BSA corona formation were examined using multiangle light scattering (MALS) dynamic (DLS). separation revealed subpopulations MC3-LNPs, while SM102-LNPs exhibited single population. Analysis shape factor indicated 0.783 SM-102-BSA 0.741 0.795 (peak 1 2) MC3-BSA, confirming interaction between LNPs BSA. Both LNP-BSA induced aggregation. Overall, demonstrates effectiveness AF4, particularly when hyphenated multidetector separating from complex biological media studying LNP-protein interactions.

Language: Английский

Citations

0
mRNA lipid nanoparticle formulation, characterization and evaluation DOI
Yutian Ma,

Rachel VanKeulen-Miller,

Owen S. Fenton

et al.

Nature Protocols, Journal Year: 2025, Volume and Issue: unknown

Published: March 11, 2025

Language: Английский

Citations

0
Exploring the Challenges of Lipid Nanoparticle Development: The In Vitro–In Vivo Correlation Gap DOI Creative Commons

Sarah Lindsay,

Muattaz Hussain,

Burcu Binici

et al.

Vaccines, Journal Year: 2025, Volume and Issue: 13(4), P. 339 - 339

Published: March 21, 2025

Background/Objectives: The development of lipid nanoparticles (LNPs) as delivery platforms for nucleic acids has revolutionised possibilities both therapeutic and vaccine applications. However, emerging studies highlight challenges in achieving reliable vitro–in vivo correlation (IVIVC), which delays the translation experimental findings into clinical This study investigates these potential discrepancies by evaluating physicochemical properties, vitro efficacy (across three commonly used cell lines), performance (mRNA expression efficacy) four LNP formulations. Methods: LNPs composed DSPC, cholesterol, a PEGylated lipid, one ionizable lipids (SM-102, ALC-0315, MC3, or C12-200) were manufactured using microfluidics. Results: All formulations exhibited comparable expected (size 70–100 nm, low PDI, near-neutral zeta potential, high mRNA encapsulation). In demonstrated variable LNP-mediated immortalised immune cells, with SM-102 inducing significantly higher protein (p < 0.05) than other cells. results revealed that ALC-0315 SM-102-based achieved without significant difference between them, while MC3- C12-200-based lower levels. As formulations, all elicited strong responses no differences among them. Conclusions: These complexities correlating outcomes demonstrate importance holistic evaluation strategies to optimise their translation.

Language: Английский

Citations

0
Mind the Age Gap: Expanding the Age Window for mRNA Vaccine Testing in Mice DOI Creative Commons

Muattaz Hussain,

Agata Ferguson-Ugorenko,

Robert Macfarlane

et al.

Vaccines, Journal Year: 2025, Volume and Issue: 13(4), P. 370 - 370

Published: March 30, 2025

Background/Objectives: Murine models play a key role in guiding formulation and immunogenicity studies across various vaccine platforms, including mRNA-based vaccines. Typically, narrow age range (6 to 8 weeks) is used these studies. Here, we investigated whether widening this could provide greater flexibility experimental design without impacting pre-clinical outcomes. Methods: To achieve this, evaluated two commonly lipid nanoparticle (LNP) formulations (based on SM102 ALC-0315 ionizable lipids) containing either firefly luciferase or ovalbumin mRNA female BALB/c mice aged 4, 8, 16 weeks. LNPs were prepared purified via microfluidics, their size, polydispersity, zeta potential, encapsulation efficiency measured. Mice injected intramuscularly, the vivo bioluminescence antibody titers measured evaluate expression profiles three groups. Results: Our findings show that 4-week-old exhibited higher protein following administration compared older groups; however, no significant differences observed between 8- 16-week-old mice. Despite initial expression, responses after prime dose lower other However, booster dose, levels comparable all Conclusions: By identifying broader window, study design, enhance data comparability studies, promote more efficient use of animal resources, while maintaining reliable representative results murine models.

Language: Английский

Citations

0