Work

First-in-Human Phase 1 Evaluation of the DegradaBALL Mesoporous Silica Nanoparticle Delivery System: An mRNA SARS-CoV-2 Vaccine Study in Healthy Korean Adult Volunteers

Year: 2026

Type: article

Study designs: Randomized Controlled Trial, Clinical Trial

Abstract: Purpose: mRNA vaccines require an effective delivery system for intracellular uptake, and alternative carriers with improved stability and tolerability remain of continued interest. This study evaluated the safety, tolerability, and exploratory immunogenicity of LEM-mR203, an mRNA SARS-CoV-2 receptor binding domain (RBD) booster vaccine formulated with DegradaBALL, a mesoporous silica nanoparticle-based delivery system developed to improve mRNA stability and enable localized delivery. Methods: In a randomized, double-blind, placebo-controlled, dose-escalation phase 1 study, a single intramuscular dose of LEM-mR203 (40 μg or 100 μg) or placebo was administered to 20 healthy Korean adult volunteers. Safety endpoints included solicited and unsolicited adverse events (AEs), serious AEs, and AEs of special interest. Exploratory immunogenicity comprised anti-RBD antibody concentrations and neutralizing antibody (Nab) titers through Day 366, together with interferon-γ (IFN-γ)/interleukin-4 (IL-4) ELISpot responses. Results: LEM-mR203 was well tolerated at both dose levels, with mild (Grade 1) injection-site reactions and infrequent solicited systemic AEs; no fever, serious AEs, or AEs of special interest were reported. Transient, asymptomatic decreases in white blood cell count occurred across active and placebo groups and resolved without sequelae. In this pre-immune cohort (85% anti-nucleocapsid reactive), anti-RBD IgG was maintained through Day 366 without a clear booster-induced increase and Nab titers against the Kappa variant (B.1.617.1) waned, consistent with known mRNA vaccine kinetics. Exploratory ELISpot results suggested an IFN-γ-oriented cellular response in the 100 μg group, without evidence of IL-4/Th2 skewing. Conclusion: A single booster dose of LEM-mR203 was well tolerated, with no major safety concerns over 366 days, and with exploratory cellular responses suggesting an IFN-γ-oriented profile without Th2 skewing. Given the small sample size and high pre-existing immunity, these findings require confirmation in larger, adequately powered studies of DegradaBALL-based mRNA vaccines.

Source: Drug Design Development and Therapy

DOI: 10.2147/dddt.s631473

Authors: Sooyoun Lee, Ki Young Huh, Kyung-Sang Yu, Dal-Hee Min, Cheolhee Won, In-Jin Jang

Institutions: Seoul National University, Seoul National University Hospital, Lemonex (South Korea)

Language: English

Topic: SARS-CoV-2 and COVID-19 Research

Subfield: Infectious Diseases

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,836