Immune Response, Influenza, Influenza Vaccines, Microbiome
Conditions
Keywords
Influenza, Influenza vaccines, Microbiome, Immune mechanism
Brief summary
This prospective, randomized, open-label clinical study aims to evaluate the immunogenicity and underlying immune mechanisms of different influenza vaccine formulations in adults aged ≥65 years. Additionally, the study investigates the role of the gut microbiome in modulating vaccine-induced immune responses and durability.
Detailed description
Despite high influenza vaccination coverage among older adults in Korea, vaccine effectiveness remains suboptimal, even during well-matched seasons. Immunosenescence and microbiome dysbiosis are believed to contribute to reduced vaccine responsiveness. This study will: * Compare immune responses induced by standard-dose, MF59-adjuvanted, and high-dose influenza vaccines * Characterize cellular and humoral immune mechanisms * Analyze gut microbiome composition and function using metagenomic approaches * Identify microbiome-derived biomarkers associated with vaccine responsiveness and durability
Interventions
BIOLOGICALStandard-Dose Influenza Vaccine
0.5 mL intramuscular injection, single dose
BIOLOGICALMF59-Adjuvanted Influenza Vaccine
0.5 mL intramuscular injection, single dose
BIOLOGICALHigh-Dose Influenza Vaccine
0.7 mL intramuscular injection, single dose
Sponsors
Korea University Guro Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
This study is a randomized, open-label, parallel-group clinical trial in which participants are assigned in a 1:1:1 ratio to receive one of three influenza vaccine formulations (standard-dose, MF59-adjuvanted, or high-dose). Each participant receives a single vaccine and is followed longitudinally for immunogenicity, safety, and microbiome analyses at predefined time points.
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Age ≥65 years * Able and willing to provide informed consent
Exclusion criteria
* Influenza vaccination within the past 6 months * Laboratory-confirmed influenza infection within the past 6 months * Immunocompromised status * Uncontrolled chronic medical conditions
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Seroconversion Rate | 4 weeks post-vaccination | ≥4-fold increase in hemagglutination inhibition (HI) antibody titers |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean Titers | Baseline, Day 7, Week 4, Month 6 | Geometric Mean Titers (GMTs) of HI antibodies |
| Cellular Immune Responses | Baseline, Day 7, Week 4 | ELISpot (IFN-γ), activated T-cell frequency (CD38, HLA-DR) |
| B Cell Responses | Baseline, Day 7, Week 4 | HA-specific B cell frequencies (A/H1N1, A/H3N2, B strains) |
| Microbiome Diversity and Composition | Baseline and Week 4 | Alpha diversity (Shannon index) Beta diversity (PERMANOVA) |
| Microbiome Biomarker Identification | Baseline, Week 4 | Taxonomic and functional markers using LEfSe analysis |
| Durability of Immune Response | Baseline, Week 4, Month 6 | Antibody decay rate (half-life analysis) |
| Safety Outcomes | Day 7, Day 30 | Solicited adverse events (within 7 days) Unsolicited adverse events (within 30 days) |
Countries
South Korea
Contacts
PRINCIPAL_INVESTIGATORJoon Young Song, MD, PhD
Korea University Guro Hospital
Outcome results
None listed