Influenza, HumanPhase 4NCT05108818
Characterization of Humoral and Cellular Immune Responses Elicited by Influenza Vaccination in Healthy Adults
A Phase 4 study testing Seasonal influenza vaccine in people with Influenza, Human, run by University of Pennsylvania at 1 site in United States.
Trial summary
Cellular and humoral immune responses before and after seasonal influenza vaccination will be assessed. Each year, up to 100 participants will be enrolled. To study age-specific differences in immune responses, participants with various years of birth will be enrolled. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Influenza, Human
- What is being tested?
- Seasonal influenza vaccine
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 700 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Oct 2021to 31 Mar 2028
- Phase
- Phase 4
- 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 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Provision of signed and dated informed consent form
- Stated willingness to comply with all study procedures and availability for all study visits
- Aged 18 years and older
- In good health based on self-reported medical conditions via an online survey
Who cannot join
- Known allergic reactions to components of the study vaccine
- Known latex allergy
- History of severe reactions following previous immunization with licensed or unlicensed influenza virus vaccines
- History of GBS within 6 weeks of receipt of a previous influenza vaccine
- Immunosuppression as a result of an underlying illness or treatment with immunosuppressive or cytotoxic drugs, or use of anticancer chemotherapy or radiation therapy within the preceding 36 months
- Treatment with immunoglobulin or another blood product within the 3 months prior to enrollment in this study
Show all 16Show fewer
- Active neoplastic disease (excluding non-melanoma skin cancer or prostate cancer that is stable in the absence of therapy) or a history of any hematological malignancy ("active" is defined as having received treatment within the past 5 years)
- Long-term (greater than 2 weeks) usage of oral or parenteral steroids, or high-dose inhaled steroids
- Administration of an influenza vaccine within 2 months prior to enrollment
- Known acute or chronic medical condition that, in the opinion of the investigator or appropriate sub-investigator, would render vaccination unsafe or would interfere with the evaluation of responses
- Participation in a study that involves an experimental agent or having received an experimental agent (other than a COVID-19 vaccine) within 1 month prior to enrollment or expecting to receive another experimental agent during the study period
- Intends to donate blood during the study period
- Any condition that would, in the opinion of the site investigator, place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol
- Pregnancy
- Known human immunodeficiency virus, hepatitis B, or hepatitis C infection
- Any condition that the principal investigator believes may interfere with successful completion of the study
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Elizabeth Drapeau, PhD, elizabeth.troisi@pennmedicine.upenn.edu
Scott Hensley, PhD, hensley@pennmedicine.upenn.edu
About this study
Cellular and humoral immune responses before and after seasonal influenza vaccination will be assessed. Each year, up to 100 participants will be enrolled. To study age-specific differences in immune responses, participants with various years of birth will be enrolled. The investigators hypothesize that humans with different birth years will mount antibody and cellular responses of different specificities following seasonal influenza vaccination.
Read the detailed description
The investigators and others have shown that the first influenza virus someone is exposed to leaves an immunological imprint that affects antibody responses to antigenically related influenza strains later in life. Year of birth can be used to predict influenza virus exposures during the first years of life. It is possible that immune responses to influenza vaccination later in life differ between people with different birth years, depending on what virus someone was "imprinted" with. This could result in birth year differences in antibody responses upon vaccination and vaccine effectiveness. However, the effect of year of birth on the specificity of humoral and cellular immune responses elicited by influenza vaccination has not been studied in depth. In this study, the investigators will measure influenza virus cellular and humoral immune responses in individuals of different birth years before and after influenza vaccination.
- Conditions
- Influenza, Human
- Being tested
- Seasonal influenza vaccine
- Medical subject headings
- Influenza, Human
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Seasonal influenza vaccineBiological
The seasonal influenza vaccine is administered intramuscularly at a dose of 15 ug of HA per component, as approved by the FDA.
| Study group | Role | What they receive |
|---|---|---|
| Influenza vaccination | Experimental | Adults will receive a seasonal, inactivated, quadrivalent influenza vaccine administered intramuscularly at a dose of 15 ug of HA per component, as approved by the FDA. Receives: Biological: Seasonal influenza vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Effect of year of birth on neutralizing antibody titers elicited by influenza vaccination
Because year of birth can be used to predict the influenza viruses circulating during the first years of life, assessing antibody responses in individuals of different birth years is one way of determining how prior exposure affects immune responses to seasonal influenza vaccination and infection. The investigators will assess how antibody responses to seasonal influenza vaccination differ in individuals across multiple age groups. Baseline serum neutralizing antibodies to post-vaccination serum neutralizing antibodies against the influenza A (H1N1 and H3N2) and influenza B viral strains that are included in the quadrivalent influenza vaccine will be compared. The investigators will compare neutralizing antibody titers between groups of individuals with different birth years. Neutralizing antibody titers against the vaccine strains will be quantified by focus reduction neutralization test (FRNT) and data will be expressed as FRNT titer.
Measured: 7 years
Secondary outcomes (6)
Changes in serum HAI antibodies in individuals of different birth years following influenza vaccination
Baseline serum antibodies will be compared to those collected after vaccination to access changes in serum hemagglutination inhibition (HAI) antibodies that block virus binding to cells. Titer will be defined as the highest dilution resulting in complete inhibition of hemagglutination in the assay. The changes measured in HAI titer between pre and post vaccination will be compared among individuals of different birth years.
Measured: 7 years
Differences in levels of HA stalk-binding antibodies in individuals of different birth years following influenza vaccination
Baseline serum antibodies will be compared to post-vaccination serum antibodies to assess differences in levels (increase or decrease) of reactive antibodies to the HA stalk of influenza viruses. Serum antibody titers will be measured by ELISA using "headless" HA to quantify serum antibodies targeting the HA stalk. Antibody titers measured in pre and post vaccination sera will be compared among individuals of different birth years. Data will be expressed as ELISA relative units.
Measured: 7 years
Differences in levels of NA-binding antibodies in individuals of different birth years following influenza vaccination
Baseline serum antibodies will be compared to post-vaccination serum antibodies to assess changes in levels (increase or decrease) of antibodies that inhibit NA activity (NA-binding antibodies) of different influenza viruses. NA activity will be measured via an enzyme-linked lectin assay (ELLA) and the amount of serum antibody present that inhibits NA activity of different influenza strains will be quantified. These titers measured in pre and post vaccination sera will be compared among individuals of different birth years. Data will be expressed as ELLA titer.
Measured: 7 years
Assessment of the frequency of circulating T follicular helper cell response to influenza vaccination in individuals of different birth years
Circulating T follicular helper cells (cTfh) with be assessed among peripheral blood mononuclear cells (PBMCs) collected at baseline and after vaccination. Frequencies, defined by percent increase or decrease, will be measured by flow cytometry-based assays. Measurement of the frequencies of cTfh in response to influenza vaccination will be compared among individuals of different birth years to determine the effect of year of birth on cTfh responses following influenza vaccination.
Measured: 7 years
Assessment of the functionality of circulating T follicular helper cell response to influenza vaccination in individuals of different birth years
Circulating T follicular helper cells (cTfh) with be assessed among peripheral blood mononuclear cells (PBMCs) collected at baseline and after vaccination. Functionality, defined by expression of specific cellular markers, will be measured by flow cytometry-based assays. Measurement of the functionality of cTfh in response to influenza vaccination will be compared among individuals of different birth years to determine the effect of year of birth on cTfh responses following influenza vaccination.
Measured: 7 years
Assessment of B cell responses to influenza vaccination in individuals of different birth years
B cells will be assessed among PBMCs collected at baseline and after vaccination. Frequencies, defined by percent increase or decrease, and clonal expansion will be measured by flow cytometry-based and high-throughput DNA sequencing assays. These metrics will be compared among individuals of different birth years to determine the effect of year of birth on B cells responses following influenza vaccination.
Measured: 7 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Nov 2021
- Study start7 Oct 2021
- Primary completion1 Apr 2027 (estimated)
- Study completion31 Mar 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Influenza, HumanStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- 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
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 700 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID), Stanford University, The Scripps Research Institute
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05108818
- Sponsor's protocol ID
- 849398
- Other IDs
- 21-0033, 75N93021C00015, Institutional Funds
- Status last verified
- Feb 2026
- First submitted
- 11 Oct 2021
- Last updated
- 9 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Protocol and statistical analysis plan may need to be shared for publication.
Study at a glance
From the registry record, last updated by the sponsor on 9 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Characterization of Humoral and Cellular Immune Responses Elicited by Influenza Vaccination in Healthy Adults
- ClinicalTrials.gov ID
- NCT05108818
- Acronym / sponsor ID
- 849398
- Conditions
- Influenza, Human
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 700 participants (estimated)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID), Stanford University, The Scripps Research Institute
- Study start
- 7 Oct 2021 (actual)
- Primary completion
- 1 Apr 2027 (estimated)
- Study completion
- 31 Mar 2028 (estimated)
- First posted
- 5 Nov 2021 (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.
Cellular and humoral immune responses before and after seasonal influenza vaccination will be assessed. Each year, up to 100 participants will be enrolled. To study age-specific differences in immune responses, participants with various years of birth will be enrolled. The investigators hypothesize that humans with different birth years will mount antibody and cellular responses of different specificities following seasonal influenza vaccination.
Detailed description
The investigators and others have shown that the first influenza virus someone is exposed to leaves an immunological imprint that affects antibody responses to antigenically related influenza strains later in life. Year of birth can be used to predict influenza virus exposures during the first years of life. It is possible that immune responses to influenza vaccination later in life differ between people with different birth years, depending on what virus someone was "imprinted" with. This could result in birth year differences in antibody responses upon vaccination and vaccine effectiveness. However, the effect of year of birth on the specificity of humoral and cellular immune responses elicited by influenza vaccination has not been studied in depth. In this study, the investigators will measure influenza virus cellular and humoral immune responses in individuals of different birth years before and after influenza vaccination.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Influenza vaccination | Experimental | Biological: Seasonal influenza vaccineAdults will receive a seasonal, inactivated, quadrivalent influenza vaccine administered intramuscularly at a dose of 15 ug of HA per component, as approved by the FDA. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Provision of signed and dated informed consent form
- Stated willingness to comply with all study procedures and availability for all study visits
- Aged 18 years and older
- In good health based on self-reported medical conditions via an online survey
Key exclusion criteria (16 listed)
- Known allergic reactions to components of the study vaccine
- Known latex allergy
- History of severe reactions following previous immunization with licensed or unlicensed influenza virus vaccines
- History of GBS within 6 weeks of receipt of a previous influenza vaccine
- Immunosuppression as a result of an underlying illness or treatment with immunosuppressive or cytotoxic drugs, or use of anticancer chemotherapy or radiation therapy within the preceding 36 months
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Seasonal influenza vaccineThe seasonal influenza vaccine is administered intramuscularly at a dose of 15 ug of HA per component, as approved by the FDA. | Biological | Influenza vaccination |
Primary outcome
Effect of year of birth on neutralizing antibody titers elicited by influenza vaccination
Time frame: 7 years
Because year of birth can be used to predict the influenza viruses circulating during the first years of life, assessing antibody responses in individuals of different birth years is one way of determining how prior exposure affects immune responses to seasonal influenza vaccination and infection. The investigators will assess how antibody responses to seasonal influenza vaccination differ in individuals across multiple age groups. Baseline serum neutralizing antibodies to post-vaccination serum neutralizing antibodies against the influenza A (H1N1 and H3N2) and influenza B viral strains that are included in the quadrivalent influenza vaccine will be compared. The investigators will compare neutralizing antibody titers between groups of individuals with different birth years. Neutralizing antibody titers against the vaccine strains will be quantified by focus reduction neutralization test (FRNT) and data will be expressed as FRNT titer.
6 secondary outcomes
Changes in serum HAI antibodies in individuals of different birth years following influenza vaccination
Time frame: 7 years
Differences in levels of HA stalk-binding antibodies in individuals of different birth years following influenza vaccination
Time frame: 7 years
Differences in levels of NA-binding antibodies in individuals of different birth years following influenza vaccination
Time frame: 7 years
Assessment of the frequency of circulating T follicular helper cell response to influenza vaccination in individuals of different birth years
Time frame: 7 years
Assessment of the functionality of circulating T follicular helper cell response to influenza vaccination in individuals of different birth years
Time frame: 7 years
Assessment of B cell responses to influenza vaccination in individuals of different birth years
Time frame: 7 years
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 9 Feb 2026.
- Individual participant dataSharing planned: Yes. Protocol and statistical analysis plan may need to be shared for publication.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Seasonal influenza vaccine in people with Influenza, Human, run by University of Pennsylvania at 1 site in United States.
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 16 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: looking for participants now, as of the sponsor's last update on 9 Feb 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 United States. 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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 Scott Hensley, PhD (215-573-3756, hensley@pennmedicine.upenn.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Effect of year of birth on neutralizing antibody titers elicited by influenza vaccination (time frame: 7 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 9 Feb 2026.