InfluenzaEOSIIVE-FNCT07357467
Effect of Oral Supplement on Influenza Vaccine Long-term Response
An observational study of Influenza and Immunosenescence, run by Tsinghua University at 1 site in China.
Trial summary
This is a follow-up study of a previously completed randomized controlled trial (NCT06827873) that investigated the effects of oral supplements on influenza vaccine response in adults aged 60-70 years. Read more about this study
- Who is it for?
- Ages 60 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Influenza, Immunosenescence
- Type of treatment
- Vaccines, Pill or oral medicine
- How many people
- 30 participants
- Where
- 1 siteChina
- Study dates
- Mar 2026to Jul 2026
- How long will I take part?
- 1 Year
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: This extended follow-up study includes participants from the original randomized controlled trial (Protocol ID: THU01-20240201; NCT06827873) conducted between February and April 2025. Thirty older adults (aged 60-70 years) were previously randomized to either the TUDCA group (n=15) or placebo group (n=15). All completed the 25-day intervention, received quadrivalent influenza vaccine on Day 3, and finished all Day 24 assessments. Participants were recruited from community health centers affiliated with the Second Affiliated Hospital of Bengbu Medical College, Anhui, China, and provided written informed consent for both the original and follow-up studies.
Who may be able to join
- Originally assigned to either the TUDCA supplementation group or placebo control group
- No influenza vaccination or other vaccines received between April 2025 and December 2025
- Willing to participate in this follow-up study and sign supplementary informed consent
- Stable health condition
Who cannot join
- Started using immunosuppressants or hormonal medications after the original study
- Experienced serious illness or hospitalization within the past month, or planning surgery soon
- Experienced fever, cold, severe diarrhea, or taken influenza antiviral medications within the past month
- Unable or unwilling to participate in blood collection
- Lost to follow-up or unable to contact
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Tsinghua University
Beijing, Beijing Municipality, 100084
Ai Zhao, PhD, +86 13811131994, aizhao18@mail.tsinghua.edu.cn
Litian Hou, Master, +86 17888846812, hlt24@mails.tsinghua.edu.cn
About this study
Official title: Effect of Oral Supplement Intervention on Influenza Vaccine Long-term Efficacy: a Follow-up Study
This is a follow-up study of a previously completed randomized controlled trial (NCT06827873) that investigated the effects of oral supplements on influenza vaccine response in adults aged 60-70 years. The original study was completed in April 2025, with participants receiving either TUDCA (Tauro Ursodesoxy Cholic Acid) supplementation, fatty acid supplementation, or placebo during influenza vaccination.
The primary objectives of this follow-up study are to:
Read more
- Evaluate the durability of vaccine-induced antibody responses approximately 8 months post-vaccination
- Assess the persistence of immune memory cells, particularly long-lived plasma cells and memory B cells
- Compare long-term immune responses between the TUDCA supplementation group and placebo group
This observational follow-up involves a single visit where participants will:
- Provide one blood sample for antibody and immune cell analysis
- No intervention or vaccination will be administered
The study will specifically focus on B cell subsets through flow cytometry analysis, including total B cells, memory B cells, plasma cells, and long-lived plasma cells. This research aims to determine whether TUDCA supplementation can enhance the durability of vaccine-induced immunity in older adults.
Read the detailed description
Influenza virus infection presents a significant global health challenge, particularly threatening the elderly population due to immunosenescence. The immune response to influenza vaccination involves a complex series of events: after vaccination, hemagglutination inhibition antibody titers peak around day 14, accompanied by the production of neutralizing antibodies and other specific antibodies. This immune response gradually stabilizes to a post-response baseline level as immune memory establishes.
The age-related decline in immune function manifests through multiple mechanisms, including: reduced production of naive T cells; decreased diversity of T cell repertoire; compromised B cell function; and altered cytokine production profiles, which all diminish vaccine response efficacy. Recent advances in immunometabolism have revealed the crucial role of specific fatty acids and bile acids in immune system modulation. Our preliminary explorations found that fatty acid intervention could significantly reduce the time required for antibody production and enhance its levels following rabies vaccination. We also noticed that serum Tauroursodeoxycholic Acid (TUDCA) was elevated in the intervention group. However, the related mechanisms remain unclear.
Besides, evidence from influenza vaccine studies reveals critical temporal dynamics: antibody titers peak at 1-1.3 months post-vaccination, decline by 3 months, yet remain elevated above baseline at 6 months. Vaccine effectiveness demonstrates time-dependent reduction from 80% at 14 days to 37% at 128 days and 46% at 180 days post-vaccination. Crucially, antibody persistence correlates with long-lived plasma cells (LLPCs), which maintain continuous antibody secretion, while memory B cells enable rapid secondary responses upon antigen re-exposure by differentiating into plasma cells and LLPCs.
Building on these findings, we hypothesized that TUDCA itself may play an active immunoregulatory role during vaccination, influencing B-cell differentiation and antibody persistence. To test this hypothesis and further characterize its potential benefits in elderly populations, we designed an extended follow-up study.
The original study (February-April 2025) demonstrated that TUDCA supplementation significantly enhanced memory B cell responses compared to placebo and fatty acid supplementation groups during the acute phase post-vaccination (Day 0-24). In this extended follow-up, conducted approximately 12 months after vaccination, participants will return for a single fasting venous blood draw (approximately 10 mL) to assess antibody titers and characterize immune-cell subsets. No further intervention or vaccination will be performed. This timepoint represents a critical window for assessing immune durability in the elderly. By quantifying long-term antibody titers and characterizing B cell subsets-particularly plasma cells and long-lived plasma cells-we will determine whether TUDCA supplementation enhances the persistence of vaccine-induced humoral and cellular immunity. This investigation addresses whether nutritional strategies can extend vaccine protection duration in older adults, where immunosenescence substantially limits both vaccine efficacy and protection longevity.
- Conditions
- Influenza, Immunosenescence
- Keywords
- Tauroursodeoxycholic Acid (TUDCA), Influenza Vaccine, Antibody, Memory B Cells, Long-lived Plasma Cells, Elderly Adults, Humoral Immunity, Nutritional Immunomodulation, Bile Acids
- Medical subject headings
- Influenza, Human
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| TUDCA Supplementation Group | Participants who received TUDCA supplementation (1000 mg/day) during the original study (February-April 2025). In the original trial, participants took 1000 mg of TUDCA (Tauroursodeoxycholic acid) dietary supplement capsules daily. Each capsule contained 500 mg of TUDCA (two capsules per serving). Participants maintained their usual lifestyle during the intervention: Day 0-Day 2 served as an adaptation period; on Day 3, they received a quadrivalent influenza vaccine, followed by continued supplementation until Day 24. This extended follow-up study involves no intervention, only a single fasting blood draw (20 mL) approximately 12 months post-vaccination to assess long-term immune responses. | |
| Placebo Group | Participants who received placebo during the original study (February-April 2025). In the original trial, participants took placebo capsules identical in appearance and smell to the TUDCA capsules. Participants maintained their usual lifestyle during the intervention: Day 0-Day 2 served as an adaptation period; on Day 3, they received a quadrivalent influenza vaccine, followed by continued placebo supplementation until Day 24. This extended follow-up study involves no intervention, only a single fasting venous blood draw (approximately 20 mL) about 12 months post-vaccination to assess long-term immune responses. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Long-term Influenza-Specific Antibody Levels Post-Vaccination
Evaluate influenza virus-specific IgG antibody levels at approximately 12 months post-vaccination to assess the durability of vaccine-induced humoral immunity. Antibody levels will be measured for all four strains contained in the quadrivalent influenza vaccine (H1N1, H3N2, B/Victoria, B/Yamagata) using ELISA or hemagglutination inhibition (HI) assay.
Measured: Day 360 (approximately 12 months post-vaccination)
Secondary outcomes (1)
B Cell Immune Memory Persistence
Assess B cell subsets through flow cytometry analysis, including Total B cells (CD19+), Memory B cells (CD19+ \& CD27+), Plasma cells (CD19+, CD38+ \& CD27+) and Long-lived plasma cells (CD19+, CD38+ \& CD138+). Compare the persistence of these immune memory cell populations between TUDCA supplementation and placebo groups to evaluate whether TUDCA enhances long-term cellular immunity.
Measured: Day 360 (approximately 12 months post-vaccination)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jan 2026
- Study startMar 2026 (estimated)
- Primary completionMay 2026 (estimated)
- Study completionJul 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for InfluenzaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 30 participants (estimated)
- Target duration
- 1 Year
Sponsor and investigators
- Lead sponsor
- Tsinghua University
- Sponsor type
- University, hospital or other
- Collaborators
- Second Affiliated Hospital of Bengbu Medical College
- Responsible party
- Principal investigator, Ai Zhao, Tsinghua University
- Investigators
- Cong Tian, Master, Study director, Second Affiliated Hospital of Bengbu Medical College
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07357467
- Sponsor's protocol ID
- THU01-20251109
- Acronym
- EOSIIVE-F
- Status last verified
- Jan 2026
- First submitted
- 12 Jan 2026
- Last updated
- 22 Jan 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Mordant FL, Price OH, Rudraraju R, Slavin MA, Marshall C, Worth LJ, Peck H, Barr IG, Sullivan SG, Subbarao K. Antibody titres elicited by the 2018 seasonal inactivated influenza vaccine decline by 3 months post-vaccination but persist for at least 6 months. Influenza Other Respir Viruses. 2023 Jan;17(1):e13072. doi: 10.1111/irv.13072. Epub 2022 Nov 30.
PubMed 36451293Ellebedy AH. Immunizing the Immune: Can We Overcome Influenza's Most Formidable Challenge? Vaccines (Basel). 2018 Sep 22;6(4):68. doi: 10.3390/vaccines6040068.
PubMed 30248996Ferdinands JM, Fry AM, Reynolds S, Petrie J, Flannery B, Jackson ML, Belongia EA. Intraseason waning of influenza vaccine protection: Evidence from the US Influenza Vaccine Effectiveness Network, 2011-12 through 2014-15. Clin Infect Dis. 2017 Mar 1;64(5):544-550. doi: 10.1093/cid/ciw816. Epub 2016 Dec 29.
PubMed 28039340
Study at a glance
From the registry record, last updated by the sponsor on 22 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Oral Supplement Intervention on Influenza Vaccine Long-term Efficacy: a Follow-up Study
- ClinicalTrials.gov ID
- NCT07357467
- Acronym / sponsor ID
- EOSIIVE-F / THU01-20251109
- Conditions
- Influenza, Immunosenescence
- Keywords
- Tauroursodeoxycholic Acid (TUDCA), Influenza Vaccine, Antibody, Memory B Cells, Long-lived Plasma Cells, Elderly Adults, Humoral Immunity, Nutritional Immunomodulation
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Tsinghua UniversityUniversity, hospital or other
- Collaborators
- Second Affiliated Hospital of Bengbu Medical College
- Study start
- Mar 2026 (estimated)
- Primary completion
- May 2026 (estimated)
- Study completion
- Jul 2026 (estimated)
- First posted
- 22 Jan 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a follow-up study of a previously completed randomized controlled trial (NCT06827873) that investigated the effects of oral supplements on influenza vaccine response in adults aged 60-70 years. The original study was completed in April 2025, with participants receiving either TUDCA (Tauro Ursodesoxy Cholic Acid) supplementation, fatty acid supplementation, or placebo during influenza vaccination.
The primary objectives of this follow-up study are to:
- Evaluate the durability of vaccine-induced antibody responses approximately 8 months post-vaccination
- Assess the persistence of immune memory cells, particularly long-lived plasma cells and memory B cells
- Compare long-term immune responses between the TUDCA supplementation group and placebo group
This observational follow-up involves a single visit where participants will:
- Provide one blood sample for antibody and immune cell analysis
- No intervention or vaccination will be administered
The study will specifically focus on B cell subsets through flow cytometry analysis, including total B cells, memory B cells, plasma cells, and long-lived plasma cells. This research aims to determine whether TUDCA supplementation can enhance the durability of vaccine-induced immunity in older adults.
Detailed description
Influenza virus infection presents a significant global health challenge, particularly threatening the elderly population due to immunosenescence. The immune response to influenza vaccination involves a complex series of events: after vaccination, hemagglutination inhibition antibody titers peak around day 14, accompanied by the production of neutralizing antibodies and other specific antibodies. This immune response gradually stabilizes to a post-response baseline level as immune memory establishes.
The age-related decline in immune function manifests through multiple mechanisms, including: reduced production of naive T cells; decreased diversity of T cell repertoire; compromised B cell function; and altered cytokine production profiles, which all diminish vaccine response efficacy. Recent advances in immunometabolism have revealed the crucial role of specific fatty acids and bile acids in immune system modulation. Our preliminary explorations found that fatty acid intervention could significantly reduce the time required for antibody production and enhance its levels following rabies vaccination. We also noticed that serum Tauroursodeoxycholic Acid (TUDCA) was elevated in the intervention group. However, the related mechanisms remain unclear.
Besides, evidence from influenza vaccine studies reveals critical temporal dynamics: antibody titers peak at 1-1.3 months post-vaccination, decline by 3 months, yet remain elevated above baseline at 6 months. Vaccine effectiveness demonstrates time-dependent reduction from 80% at 14 days to 37% at 128 days and 46% at 180 days post-vaccination. Crucially, antibody persistence correlates with long-lived plasma cells (LLPCs), which maintain continuous antibody secretion, while memory B cells enable rapid secondary responses upon antigen re-exposure by differentiating into plasma cells and LLPCs.
Building on these findings, we hypothesized that TUDCA itself may play an active immunoregulatory role during vaccination, influencing B-cell differentiation and antibody persistence. To test this hypothesis and further characterize its potential benefits in elderly populations, we designed an extended follow-up study.
The original study (February-April 2025) demonstrated that TUDCA supplementation significantly enhanced memory B cell responses compared to placebo and fatty acid supplementation groups during the acute phase post-vaccination (Day 0-24). In this extended follow-up, conducted approximately 12 months after vaccination, participants will return for a single fasting venous blood draw (approximately 10 mL) to assess antibody titers and characterize immune-cell subsets. No further intervention or vaccination will be performed. This timepoint represents a critical window for assessing immune durability in the elderly. By quantifying long-term antibody titers and characterizing B cell subsets-particularly plasma cells and long-lived plasma cells-we will determine whether TUDCA supplementation enhances the persistence of vaccine-induced humoral and cellular immunity. This investigation addresses whether nutritional strategies can extend vaccine protection duration in older adults, where immunosenescence substantially limits both vaccine efficacy and protection longevity.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 1 Year
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| TUDCA Supplementation Group | – | –Participants who received TUDCA supplementation (1000 mg/day) during the original study (February-April 2025). In the original trial, participants took 1000 mg of TUDCA (Tauroursodeoxycholic acid) dietary supplement capsules daily. Each capsule contained 500 mg of TUDCA (two capsules per serving). Participants maintained their usual lifestyle during the intervention: Day 0-Day 2 served as an adaptation period; on Day 3, they received a quadrivalent influenza vaccine, followed by continued supplementation until Day 24. This extended follow-up study involves no intervention, only a single fasting blood draw (20 mL) approximately 12 months post-vaccination to assess long-term immune responses. |
| Placebo Group | – | –Participants who received placebo during the original study (February-April 2025). In the original trial, participants took placebo capsules identical in appearance and smell to the TUDCA capsules. Participants maintained their usual lifestyle during the intervention: Day 0-Day 2 served as an adaptation period; on Day 3, they received a quadrivalent influenza vaccine, followed by continued placebo supplementation until Day 24. This extended follow-up study involves no intervention, only a single fasting venous blood draw (approximately 20 mL) about 12 months post-vaccination to assess long-term immune responses. |
Who may qualify
- Ages
- 60 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- This extended follow-up study includes participants from the original randomized controlled trial (Protocol ID: THU01-20240201; NCT06827873) conducted between February and April 2025. Thirty older adults (aged 60-70 years) were previously randomized to either the TUDCA group (n=15) or placebo group (n=15). All completed the 25-day intervention, received quadrivalent influenza vaccine on Day 3, and finished all Day 24 assessments. Participants were recruited from community health centers affiliated with the Second Affiliated Hospital of Bengbu Medical College, Anhui, China, and provided written informed consent for both the original and follow-up studies.
Key inclusion criteria (4 listed)
- Originally assigned to either the TUDCA supplementation group or placebo control group
- No influenza vaccination or other vaccines received between April 2025 and December 2025
- Willing to participate in this follow-up study and sign supplementary informed consent
- Stable health condition
Key exclusion criteria (5 listed)
- Started using immunosuppressants or hormonal medications after the original study
- Experienced serious illness or hospitalization within the past month, or planning surgery soon
- Experienced fever, cold, severe diarrhea, or taken influenza antiviral medications within the past month
- Unable or unwilling to participate in blood collection
- Lost to follow-up or unable to contact
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Long-term Influenza-Specific Antibody Levels Post-Vaccination
Time frame: Day 360 (approximately 12 months post-vaccination)
Evaluate influenza virus-specific IgG antibody levels at approximately 12 months post-vaccination to assess the durability of vaccine-induced humoral immunity. Antibody levels will be measured for all four strains contained in the quadrivalent influenza vaccine (H1N1, H3N2, B/Victoria, B/Yamagata) using ELISA or hemagglutination inhibition (HI) assay.
1 secondary outcome
B Cell Immune Memory Persistence
Time frame: Day 360 (approximately 12 months post-vaccination)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jan 2026.
- Background: PubMed 36451293Mordant FL, Price OH, Rudraraju R, Slavin MA, Marshall C, Worth LJ, Peck H, Barr IG, Sullivan SG, Subbarao K. Antibody titres elicited by the 2018 seasonal inactivated influenza vaccine decline by 3 months post-vaccination but persist for at least 6 months. Influenza Other Respir Viruses. 2023 Jan;17(1):e13072. doi: 10.1111/irv.13072. Epub 2022 Nov 30.
- Background: PubMed 30248996Ellebedy AH. Immunizing the Immune: Can We Overcome Influenza's Most Formidable Challenge? Vaccines (Basel). 2018 Sep 22;6(4):68. doi: 10.3390/vaccines6040068.
- Background: PubMed 28039340Ferdinands JM, Fry AM, Reynolds S, Petrie J, Flannery B, Jackson ML, Belongia EA. Intraseason waning of influenza vaccine protection: Evidence from the US Influenza Vaccine Effectiveness Network, 2011-12 through 2014-15. Clin Infect Dis. 2017 Mar 1;64(5):544-550. doi: 10.1093/cid/ciw816. Epub 2016 Dec 29.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Cong Tian, Master study director
Second Affiliated Hospital of Bengbu Medical College
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Influenza and Immunosenescence, run by Tsinghua University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 22 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ai Zhao, PhD (+86 13811131994, aizhao18@mail.tsinghua.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Long-term Influenza-Specific Antibody Levels Post-Vaccination (time frame: Day 360 (approximately 12 months post-vaccination)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07357467, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jan 2026.