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
- 1Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea
- 2Department of Chemistry, Seoul National University, Seoul, Republic of Korea
- 3Lemonex Inc., Institute of Biotherapeutics Convergence Technology, Seoul, Republic of Korea
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.
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BibTeX
@article{lee2026firstinhuman,
title = {{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}},
author = {Sooyoun Lee and Ki Young Huh and Kyung-Sang Yu and Dal-Hee Min and Cheolhee Won and In-Jin Jang},
journal = {Drug Design, Development and Therapy},
year = {2026},
month = oct,
doi = {10.2147/dddt.s631473},
url = {https://doi.org/10.2147/dddt.s631473},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - 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
AU - Sooyoun Lee
AU - Ki Young Huh
AU - Kyung-Sang Yu
AU - Dal-Hee Min
AU - Cheolhee Won
AU - In-Jin Jang
PY - 2026
DA - 2026/10/30
JO - Drug Design, Development and Therapy
DO - 10.2147/dddt.s631473
UR - https://doi.org/10.2147/dddt.s631473
AB - 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.
SN - 1177-8881
ER -