Healthy VolunteerPhase 2NCT04025580
Systems Analyses of the Immune Response to the Seasonal Influenza Vaccine
A Phase 2 study testing Flucelvax, Fluvirin and Fluzone High Dose in people with Healthy Volunteer, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
Background: Vaccines help prevent disease by causing the body to have an immune response. Many parts of this response happen in the blood. This response happens over days and weeks after getting the vaccine. Researchers want to how the blood changes over time in response to vaccines. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Healthy Volunteer
- What is being tested?
- Flucelvax, Fluvirin and Fluzone High Dose
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 98 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Oct 2019to 31 Jan 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Individuals must meet all of the following criteria to be eligible for study participation:
- Aged 18 years and older (no upper age limit).
- Able to provide informed consent.
- Willing to have samples and data stored for future research.
- Able to proficiently speak, read, and write English.
Who cannot join
- Individuals meeting any of the following criteria will be excluded from study participation:
- CBC with differential, lymphocyte phenotyping with T, B, and natural killer cells (TBNK), acute care, mineral, and hepatic panels, anti-CMV immunoglobulin (Ig) G and IgM, and/or anti-Epstein-Barr virus (EBV) antibody panel values outside of the NIH Department of Laboratory Medicine normal reference ranges and deemed clinically significant by the PI at the time of screening.
- Positive result for anti-HIV 1/2 antibody, antibody to hepatitis B surface antigen, or anti-hepatitis C virus antibody screening at the time of screening.
- Prior receipt of a current seasonal influenza vaccine (for the season of participation).
- History of allergy or hypersensitivity to any components of the study vaccine (e.g., egg protein, latex).
- History of severe reactions to vaccines.
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- Use of an oral glucocorticoid within the past 30 days.
- Receipt of a live-attenuated vaccine within the past 30 days.
- Receipt of any experimental vaccine.
- Receipt of any other type of vaccine (non-live and non-experimental, e.g., tetanus, diphtheria, and pertussis [TDaP]) within the past 14 days.
- Planned vaccination before day 100 after study vaccination.
- Current or recent use (within the past 90 days) of immunoglobulin therapy.
- Surgery within the past 8 weeks, or planned surgery before day 100.
- Current (within the past 30 days) treatment for active malignancy.
- Cancer chemotherapy in the past 5 years.
- Administration of any blood products within 90 days of the screening, or planned administration before day 100.
- History of parasitic, amebic, fungal, or mycobacterial infections within the past 1 year with the exception of tinea pedis and onychomycosis.
- Diabetes mellitus.
- History of autoimmune or autoinflammatory disease.
- History of a bleeding disorder.
- Current use (within the past 30 days) of illicit drugs (per subject report).
- Current use (within the past 30 days) of nicotine-containing products, including cigarettes and chewing tobacco, nicotine patches, gum, electronic cigarettes, etc.
- Current alcohol use disorders (criteria per Diagnostic and Statistical Manual of Mental Disorders, fifth edition), within the past 30 days.
- Serious, ongoing, uncontrolled infection within the past 30 days as per the judgement of the PI.
- History of Guillain-Barre syndrome (GBS).
- BMI greater than or equal to 30.
- Known or suspected immunodeficiency within 1 year, including documented HIV infection.
- Pregnancy or planning to become pregnant during the study period. (Women of childbearing potential must have a negative urine or serum pregnancy test at screening.)
- Presence of conditions that, in the judgment of the PI, may put the individual at undue risk or compromise the scientific objectives of the study.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Background:
Vaccines help prevent disease by causing the body to have an immune response. Many parts of this response happen in the blood. This response happens over days and weeks after getting the vaccine. Researchers want to how the blood changes over time in response to vaccines. They want to find out why vaccines work better for some people than for others. This could help make more effective vaccines.
Read more
Objective:
To learn about how the body responds to vaccines.
Eligibility:
Healthy people ages 18 and older
Design:
Participants will be screened with a medical history, physical exam, and blood and urine tests.
Participants will have 9 visits over 6 months. All visits will include blood tests and a physical exam.
Participants will have the first visit 1 week before they get the vaccine.
Participants will get the flu vaccine at the second visit. The vaccine will be injected into the muscle of the upper arm with a needle. They will be watched for side effects for 15 minutes.
Participants will have the next 2 visits exactly 1 day and 1 week after they get the vaccine. They will have the other 5 visits about 14, 28, 70, and 100 days after they get the vaccine.
Participants will take email questionnaires about whether they had any side effects.
Participants may have optional extra study visits. These will be no more than once a month for up to 1 year after they get the vaccine. Optionally, they can also repeat the study each year through the 2023 - 2024 flu season
Read the detailed description
Certain functions of the immune system are revealed only when the immune system is challenged. When a person is vaccinated, a coordinated response results: activation and interaction of distinct innate and adaptive immune cell populations and pathways, culminating in the formation of germinal centers from which antibody-producing plasma cells and memory B cells derive. By taking measurements at various time points before and after vaccination, we can build a comprehensive picture of how the immune system responds to a vaccine challenge.
The seasonal influenza vaccination provides an excellent model of coordinated immune activity involving innate and adaptive responses, as demonstrated in a past NIH study in 2009-2011; however, scientific advances and the possibility of multi-season responses in individuals warrant a new follow-up study with more comprehensive sampling. This is an open-label, prospective, exploratory study to assess the baseline and post-vaccination immune responses of healthy volunteers to an approved seasonal influenza vaccine. Subjects will undergo baseline blood collections on day -7 and on day 0 before receiving the study vaccine. After vaccination, blood will be collected on days 1, 7, 14, 28, 70, and 100. Optionally, subjects may also give blood once a month, as requested, up until 1 year after vaccination. Blood samples will be used to assess short- and long-term immunological effects of immunization. Evaluations will include vaccine antibody titers. Additional evaluations may include peripheral immune cell phenotyping, RNA sequencing (RNA-seq) of whole blood and defined peripheral blood cell subsets, and measurement of serum proteins and antibodies. Subjects may optionally provide stool samples at some visits for exploratory microbiome assessment. Additionally, subjects may optionally continue study participation annually through the 2023-24 influenza season.
The goal of this protocol is to use the collective information gathered across all healthy volunteers to understand how the immune system works as a whole.
- Conditions
- Healthy Volunteer
- Being tested
- Flucelvax, Fluvirin, Fluzone High Dose
- Keywords
- COVID-19, Systems Biology, Immunology
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FlucelvaxBiological
Seasonal influenza vaccine
FluvirinBiological
Seasonal influenza vaccine
Fluzone High DoseBiological
Seasonal influenza vaccine for adults ages 65 and older
| Study group | Role | What they receive |
|---|---|---|
| Flucelvax, Fluvirin, or Fluzone High Dose | Experimental | Healthy Volunteer between ages 18-65 receiving Flucelvax Receives: Biological: Flucelvax; Biological: Fluvirin; Biological: Fluzone High Dose |
What is being measured
The primary outcome is the main question the study is designed to answer.
Microneutralization Titers
Change in antibody titer response to vaccination, as measured by microneutralization titers at day 0 and day 70 and its relationship with novel baseline biomarkers
Measured: Day 0 and Day 28 Reported in Manuscript
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jul 2019
- Study start2 Oct 2019
- Primary completion31 Jan 2023
- Study completion31 Jan 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Healthy VolunteerStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The 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 2
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 98 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Rachel D Sparks, M.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04025580
- Sponsor's protocol ID
- 190126
- Other IDs
- 19-I-0126
- Status last verified
- 31 Jan 2023
- First submitted
- 18 Jul 2019
- Last updated
- 2 Jan 2024
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Sparks R, Lau WW, Liu C, Han KL, Vrindten KL, Sun G, Cox M, Andrews SF, Bansal N, Failla LE, Manischewitz J, Grubbs G, King LR, Koroleva G, Leimenstoll S, Snow L; OP11 Clinical Staff; Chen J, Tang J, Mukherjee A, Sellers BA, Apps R, McDermott AB, Martins AJ, Bloch EM, Golding H, Khurana S, Tsang JS. Influenza vaccination reveals sex dimorphic imprints of prior mild COVID-19. Nature. 2023 Feb;614(7949):752-761. doi: 10.1038/s41586-022-05670-5. Epub 2023 Jan 4.
PubMed 36599369
Study at a glance
From the registry record, last updated by the sponsor on 2 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Systems Analyses of the Immune Response to the Seasonal Influenza Vaccine
- ClinicalTrials.gov ID
- NCT04025580
- Acronym / sponsor ID
- 190126
- Conditions
- Healthy Volunteer
- Keywords
- COVID-19, Systems Biology, Immunology
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 98 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 2 Oct 2019 (actual)
- Primary completion
- 31 Jan 2023 (actual)
- Study completion
- 31 Jan 2023 (actual)
- First posted
- 19 Jul 2019 (actual)
- Results
- Posted 2 Jan 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
Vaccines help prevent disease by causing the body to have an immune response. Many parts of this response happen in the blood. This response happens over days and weeks after getting the vaccine. Researchers want to how the blood changes over time in response to vaccines. They want to find out why vaccines work better for some people than for others. This could help make more effective vaccines.
Objective:
To learn about how the body responds to vaccines.
Eligibility:
Healthy people ages 18 and older
Design:
Participants will be screened with a medical history, physical exam, and blood and urine tests.
Participants will have 9 visits over 6 months. All visits will include blood tests and a physical exam.
Participants will have the first visit 1 week before they get the vaccine.
Participants will get the flu vaccine at the second visit. The vaccine will be injected into the muscle of the upper arm with a needle. They will be watched for side effects for 15 minutes.
Participants will have the next 2 visits exactly 1 day and 1 week after they get the vaccine. They will have the other 5 visits about 14, 28, 70, and 100 days after they get the vaccine.
Participants will take email questionnaires about whether they had any side effects.
Participants may have optional extra study visits. These will be no more than once a month for up to 1 year after they get the vaccine. Optionally, they can also repeat the study each year through the 2023 - 2024 flu season
Detailed description
Certain functions of the immune system are revealed only when the immune system is challenged. When a person is vaccinated, a coordinated response results: activation and interaction of distinct innate and adaptive immune cell populations and pathways, culminating in the formation of germinal centers from which antibody-producing plasma cells and memory B cells derive. By taking measurements at various time points before and after vaccination, we can build a comprehensive picture of how the immune system responds to a vaccine challenge.
The seasonal influenza vaccination provides an excellent model of coordinated immune activity involving innate and adaptive responses, as demonstrated in a past NIH study in 2009-2011; however, scientific advances and the possibility of multi-season responses in individuals warrant a new follow-up study with more comprehensive sampling. This is an open-label, prospective, exploratory study to assess the baseline and post-vaccination immune responses of healthy volunteers to an approved seasonal influenza vaccine. Subjects will undergo baseline blood collections on day -7 and on day 0 before receiving the study vaccine. After vaccination, blood will be collected on days 1, 7, 14, 28, 70, and 100. Optionally, subjects may also give blood once a month, as requested, up until 1 year after vaccination. Blood samples will be used to assess short- and long-term immunological effects of immunization. Evaluations will include vaccine antibody titers. Additional evaluations may include peripheral immune cell phenotyping, RNA sequencing (RNA-seq) of whole blood and defined peripheral blood cell subsets, and measurement of serum proteins and antibodies. Subjects may optionally provide stool samples at some visits for exploratory microbiome assessment. Additionally, subjects may optionally continue study participation annually through the 2023-24 influenza season.
The goal of this protocol is to use the collective information gathered across all healthy volunteers to understand how the immune system works as a whole.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Flucelvax, Fluvirin, or Fluzone High Dose | Experimental | Biological: Flucelvax, Biological: Fluvirin, Biological: Fluzone High DoseHealthy Volunteer between ages 18-65 receiving Flucelvax |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Individuals must meet all of the following criteria to be eligible for study participation:
- Aged 18 years and older (no upper age limit).
- Able to provide informed consent.
- Willing to have samples and data stored for future research.
- Able to proficiently speak, read, and write English.
Key exclusion criteria (29 listed)
- Individuals meeting any of the following criteria will be excluded from study participation:
- CBC with differential, lymphocyte phenotyping with T, B, and natural killer cells (TBNK), acute care, mineral, and hepatic panels, anti-CMV immunoglobulin (Ig) G and IgM, and/or anti-Epstein-Barr virus (EBV) antibody panel values outside of the NIH Department of Laboratory Medicine normal reference ranges and deemed clinically significant by the PI at the time of screening.
- Positive result for anti-HIV 1/2 antibody, antibody to hepatitis B surface antigen, or anti-hepatitis C virus antibody screening at the time of screening.
- Prior receipt of a current seasonal influenza vaccine (for the season of participation).
- History of allergy or hypersensitivity to any components of the study vaccine (e.g., egg protein, latex).
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 |
|---|---|---|
| FlucelvaxSeasonal influenza vaccine | Biological | Flucelvax, Fluvirin, or Fluzone High Dose |
| FluvirinSeasonal influenza vaccine | Biological | Flucelvax, Fluvirin, or Fluzone High Dose |
| Fluzone High DoseSeasonal influenza vaccine for adults ages 65 and older | Biological | Flucelvax, Fluvirin, or Fluzone High Dose |
Primary outcome
Microneutralization Titers
Time frame: Day 0 and Day 28 Reported in Manuscript
Change in antibody titer response to vaccination, as measured by microneutralization titers at day 0 and day 70 and its relationship with novel baseline biomarkers
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jan 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 36599369Sparks R, Lau WW, Liu C, Han KL, Vrindten KL, Sun G, Cox M, Andrews SF, Bansal N, Failla LE, Manischewitz J, Grubbs G, King LR, Koroleva G, Leimenstoll S, Snow L; OP11 Clinical Staff; Chen J, Tang J, Mukherjee A, Sellers BA, Apps R, McDermott AB, Martins AJ, Bloch EM, Golding H, Khurana S, Tsang JS. Influenza vaccination reveals sex dimorphic imprints of prior mild COVID-19. Nature. 2023 Feb;614(7949):752-761. doi: 10.1038/s41586-022-05670-5. Epub 2023 Jan 4.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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Screening Protocol
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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.
Rachel D Sparks, M.D. principal investigator
National Institute of Allergy and Infectious Diseases (NIAID)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Flucelvax, Fluvirin and Fluzone High Dose in people with Healthy Volunteer, run by National Institute of Allergy and Infectious Diseases (NIAID) 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 29 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: finished, as of the sponsor's last update on 2 Jan 2024. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Jan 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Microneutralization Titers (time frame: Day 0 and Day 28 Reported in Manuscript). 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 NCT04025580, which also lists 1 linked publication.
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 2 Jan 2024.