InfluenzaPhase 4NCT04101838
B Cell and Antibody Response to Seasonal Influenza Vaccines in Younger and Older Adults
A Phase 4 study testing Fluzone, Flucelvax and Fluzone High-Dose in people with Influenza, run by University of Alabama at Birmingham at 1 site in United States.
Trial summary
This study will examine how various FDA-approved seasonal influenza vaccine types, used in a manner consistent with their approved use, impact the characteristics of influenza specific antibodies in humans, and how these responses differ based on age and prior immunization history. Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Influenza
- What is being tested?
- Fluzone, Flucelvax and Fluzone High-Dose
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Apr 2021to May 2027
- 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 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Participation in ancillary clinical research study
- Able to give informed consent
- Age 18-50 years old for Arm 1 and Arm 2
- Age 65-80 years old for Arm 3, Arm 4, and Arm 5
- Weight of at least 110 lbs as determined by self-reporting
Who cannot join
- Inability to give informed consent
- Refusal or inability to have blood drawn or participate in study procedures
- Previous adverse reaction to influenza vaccine or medical history contraindicated for receiving influenza vaccine, including but not limited to:
- History of Guillain-Barre Syndrome
- History of egg allergy
- History of gelatin allergy
Show all 33Show fewer
- History of moderate to severe illness with or without fever within 6 weeks of receipt of influenza vaccine
- Previous receipt of influenza vaccine outside of study within current season
- Bleeding disorder diagnosed by a doctor (eg, factor deficiency, coagulopathy, or platelet disorder requiring special precautions)
- Participant has any medical, psychiatric, or social condition, or occupational or other responsibility that, in the judgement of the investigator would interfere with, or serve as a contraindication to the planned procedure(s).
- These following criteria are used for scientific reasons, and not safety reasons. Specifically, the criteria are used to obtain a population that is healthy and less likely to have conditions that may influence the immune system:
- No recent respiratory infections in the past 4 weeks at time of vaccination
- Malignancy
- Evidence of Inflammation: Systemic Lupus Erythematosis, Rheumatoid Arthritis, Polymyositis, Dermatomyositis, Scleroderma, Crohn's Disease, Ulcerative Colitis.
- Lymphoproliferative Disorder
- Known Immunodeficiency
- Myocardial Infarction <6 months
- Cerebral Vascular Accident
- Peripheral Vascular Disease- recannulation <6months
- Cardiac Insufficiency - congestive heart failure
- Hypertension with increased blood urea nitrogen (BUN)
- Renal Failure
- Dementia
- Alcoholism (defined as >17 drinks/week)
- Drug Abuse (excluding marijuana)
- HIV positive
- History of hepatitis
- History of immunization within 4 weeks of study participation or plan to receive non- IIV vaccination within 4 weeks of receiving IIV
- Moderate to severe illness at time of enrollment
- Donations of blood in the 8 weeks prior to enrollment which, combined with expected volumes to be drawn for this study, would exceed 450 mL in an 8 week period.
- Current pregnancy at time of enrollment or pregnancy within last 4 months
- Active or planned breastfeeding during study participation
- Psychiatric condition that precludes compliance with the protocol. Specifically excluded are persons with psychoses within the past 3 years, ongoing risk for suicide, or history of suicide attempt or gesture within the past 3 years.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Alabama at Birmingham
Birmingham, Alabama, 35294
About this study
This study will examine how various FDA-approved seasonal influenza vaccine types, used in a manner consistent with their approved use, impact the characteristics of influenza specific antibodies in humans, and how these responses differ based on age and prior immunization history.
Read the detailed description
This study is particularly focused on studying antibodies, a protein in blood that react with foreign substances (such as bacteria and viruses) to help eliminate them. This study will examine antibodies and the cells that they are produced by, B cells that develop in response to the influenza vaccine.
The majority of antibodies that develop following seasonal influenza vaccine are highly specific for particular influenza strain that comprises the influenza vaccine, necessitating the annual reformulation of the influenza vaccine to match strains expected to be in circulation for the upcoming season. This is problematic, and strategies to develop an influenza vaccine that can promote the robust and persistent development of antibodies that are effective against a wide range of influenza strains are needed. One potential strategy is to promote antibody responses targeting the neuraminidase (NA) protein of influenza. NA is more highly conserved across influenza viruses as compared to the hemagglutinin (HA) protein which is the major component of the influenza vaccine. Thus understanding how differences in seasonal influenza vaccines may influence the quality and breadth of HA and NA specific antibodies is of importance in the development of more effective influenza vaccines.
There are several FDA-approved seasonal inactivated influenza vaccines (IIVs) and it remains unknown the extent to which they may induce HA and NA-specific B cells and antibodies, and particularly those that may have broad protective activity against influenza. Differences in the various seasonal IIVs, such as how they were produced, their dose, and the immune stimulating components (adjuvant) they contain may influence the HA and NA-specific response. The two major types of seasonal IIV approved for adults are IIV that is comprised of inactivated influenza virus that was grown in chicken eggs (e.g. Sanofi Fluzone, IIV), and the other comprised of inactivated influenza virus that was grown in cell culture (e.g. Seqirus Flucelvax, cc-IIV). Additionally, for adults 65 years and older, High Dose Fluzone (HD-IIV3), and Sequris Fluad IIV, which includes an adjuvant (a-IIV3). This study will evaluate the relative induction of HA and NA-specific antibodies and B cells from adults immunized with these various seasonal influenza vaccines, and how these responses may change after each year, and differ in older adults who may have a different past exposure history to influenza compared to younger adults. The seasonal influenza vaccines will be given as standard of care, in populations they are approved for, and administered in approved dose and route.
- Conditions
- Influenza
- Being tested
- Fluzone, Flucelvax, Fluzone High-Dose, Fluad
- Keywords
- 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.
FluzoneDrug
Also called influenza vaccine
inactivated seasonal influenza vaccine
FlucelvaxDrug
Also called influenza vaccine
inactivated seasonal influenza vaccine
Fluzone High-DoseDrug
Also called high dose influenza vaccine
inactivated seasonal influenza vaccine
FluadDrug
Also called adjuvanted influenza vaccine
inactivated seasonal influenza vaccine
| Study group | Role | What they receive |
|---|---|---|
| Fluzone Younger | Active comparator | 10 adults 18-50 years old, will receive a single dose of the Fluzone influenza vaccine each year for two sequential years Receives: Drug: Fluzone |
| Flucelvax | Active comparator | 10 adults 18-50 years old, will receive a single dose of the Flucelvax influenza vaccine each year for two sequential years Receives: Drug: Flucelvax |
| Fluzone Older | Active comparator | 10 adults 65-80 years old, will receive a single dose of the Fluzone influenza vaccine Receives: Drug: Fluzone |
| Fluzone High Dose | Active comparator | 10 adults 65-80 years old, will receive a single dose of the Fluzone High-Dose influenza vaccine Receives: Drug: Fluzone High-Dose |
| Fluad | Active comparator | 10 adults 65-80 years old, will receive a single dose of the Fluad influenza vaccine Receives: Drug: Fluad |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hemagglutinin antibody
hemagglutinin plasma antibody titer
Measured: 3 months after vaccination
Neuraminidase antibody
Neuraminidase plasma antibody titer
Measured: 3 months after vaccination
Secondary outcomes (2)
Hemagglutinin Memory B cell ELISPOT Response
hemagglutinin-specific memory B cells
Measured: 3 months after vaccination
Neuraminidase Memory B cell ELISPOT Response
Neuraminidase-specific memory B cells
Measured: 3 months after vaccination
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Sep 2019
- Study start1 Apr 2021
- Primary completion11 May 2026
- Study completionMay 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for InfluenzaStudies of the same condition, open and under way.
- More trials run by University of Alabama at BirminghamThe 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, James Kobie, University of Alabama at Birmingham
- Investigators
- James J Kobie, PhD, Principal investigator, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04101838
- Sponsor's protocol ID
- IRB-300003914
- Other IDs
- UAB
- Status last verified
- May 2026
- First submitted
- 22 Sep 2019
- Last updated
- 14 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- B Cell and Antibody Response to Seasonal Influenza Vaccines in Younger and Older Adults
- ClinicalTrials.gov ID
- NCT04101838
- Acronym / sponsor ID
- IRB-300003914
- Conditions
- Influenza
- Keywords
- vaccine
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- Study start
- 1 Apr 2021 (actual)
- Primary completion
- 11 May 2026 (actual)
- Study completion
- May 2027 (estimated)
- First posted
- 24 Sep 2019 (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 study will examine how various FDA-approved seasonal influenza vaccine types, used in a manner consistent with their approved use, impact the characteristics of influenza specific antibodies in humans, and how these responses differ based on age and prior immunization history.
Detailed description
This study is particularly focused on studying antibodies, a protein in blood that react with foreign substances (such as bacteria and viruses) to help eliminate them. This study will examine antibodies and the cells that they are produced by, B cells that develop in response to the influenza vaccine.
The majority of antibodies that develop following seasonal influenza vaccine are highly specific for particular influenza strain that comprises the influenza vaccine, necessitating the annual reformulation of the influenza vaccine to match strains expected to be in circulation for the upcoming season. This is problematic, and strategies to develop an influenza vaccine that can promote the robust and persistent development of antibodies that are effective against a wide range of influenza strains are needed. One potential strategy is to promote antibody responses targeting the neuraminidase (NA) protein of influenza. NA is more highly conserved across influenza viruses as compared to the hemagglutinin (HA) protein which is the major component of the influenza vaccine. Thus understanding how differences in seasonal influenza vaccines may influence the quality and breadth of HA and NA specific antibodies is of importance in the development of more effective influenza vaccines.
There are several FDA-approved seasonal inactivated influenza vaccines (IIVs) and it remains unknown the extent to which they may induce HA and NA-specific B cells and antibodies, and particularly those that may have broad protective activity against influenza. Differences in the various seasonal IIVs, such as how they were produced, their dose, and the immune stimulating components (adjuvant) they contain may influence the HA and NA-specific response. The two major types of seasonal IIV approved for adults are IIV that is comprised of inactivated influenza virus that was grown in chicken eggs (e.g. Sanofi Fluzone, IIV), and the other comprised of inactivated influenza virus that was grown in cell culture (e.g. Seqirus Flucelvax, cc-IIV). Additionally, for adults 65 years and older, High Dose Fluzone (HD-IIV3), and Sequris Fluad IIV, which includes an adjuvant (a-IIV3). This study will evaluate the relative induction of HA and NA-specific antibodies and B cells from adults immunized with these various seasonal influenza vaccines, and how these responses may change after each year, and differ in older adults who may have a different past exposure history to influenza compared to younger adults. The seasonal influenza vaccines will be given as standard of care, in populations they are approved for, and administered in approved dose and route.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Fluzone Younger | Active comparator | Drug: Fluzone10 adults 18-50 years old, will receive a single dose of the Fluzone influenza vaccine each year for two sequential years |
| Flucelvax | Active comparator | Drug: Flucelvax10 adults 18-50 years old, will receive a single dose of the Flucelvax influenza vaccine each year for two sequential years |
| Fluzone Older | Active comparator | Drug: Fluzone10 adults 65-80 years old, will receive a single dose of the Fluzone influenza vaccine |
| Fluzone High Dose | Active comparator | Drug: Fluzone High-Dose10 adults 65-80 years old, will receive a single dose of the Fluzone High-Dose influenza vaccine |
| Fluad | Active comparator | Drug: Fluad10 adults 65-80 years old, will receive a single dose of the Fluad influenza vaccine |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Participation in ancillary clinical research study
- Able to give informed consent
- Age 18-50 years old for Arm 1 and Arm 2
- Age 65-80 years old for Arm 3, Arm 4, and Arm 5
- Weight of at least 110 lbs as determined by self-reporting
Key exclusion criteria (33 listed)
- Inability to give informed consent
- Refusal or inability to have blood drawn or participate in study procedures
- Previous adverse reaction to influenza vaccine or medical history contraindicated for receiving influenza vaccine, including but not limited to:
- Previous receipt of influenza vaccine outside of study within current season
- Bleeding disorder diagnosed by a doctor (eg, factor deficiency, coagulopathy, or platelet disorder requiring special precautions)
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 |
|---|---|---|
| FluzoneAlso: influenza vaccineinactivated seasonal influenza vaccine | Drug | Fluzone Older, Fluzone Younger |
| FlucelvaxAlso: influenza vaccineinactivated seasonal influenza vaccine | Drug | Flucelvax |
| Fluzone High-DoseAlso: high dose influenza vaccineinactivated seasonal influenza vaccine | Drug | Fluzone High Dose |
| FluadAlso: adjuvanted influenza vaccineinactivated seasonal influenza vaccine | Drug | Fluad |
Primary outcome
Hemagglutinin antibody
Time frame: 3 months after vaccination
hemagglutinin plasma antibody titer
Neuraminidase antibody
Time frame: 3 months after vaccination
Neuraminidase plasma antibody titer
2 secondary outcomes
Hemagglutinin Memory B cell ELISPOT Response
Time frame: 3 months after vaccination
Neuraminidase Memory B cell ELISPOT Response
Time frame: 3 months after 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 14 May 2026.
- 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. This study is not recruiting at the moment.
James J Kobie, PhD principal investigator
University of Alabama at Birmingham
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 Fluzone, Flucelvax and Fluzone High-Dose in people with Influenza, run by University of Alabama at Birmingham 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 5 inclusion and 33 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: under way, not looking for participants, as of the sponsor's last update on 14 May 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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hemagglutinin antibody (time frame: 3 months after vaccination). The study lists 2 primary outcomes in all. 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 14 May 2026.