- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03686514
The Impact of Imprinting and Repeated Influenza Vaccination on Adaptive Immunity, Transcriptomics, and Metabolomics (FLU2)
Study Overview
Detailed Description
Seasonal influenza outbreaks continue to cause substantial disease burden, with an estimated 3-5 million cases of severe illness, and 250,000 to 500,000 deaths worldwide each year. In the United States, the Centers for Disease Control and Prevention (CDC) reports that influenza has resulted in 9.2-35.6 million illnesses with 12,000-56,000 deaths annually since 2010. There is an urgent need to better understand the immunologic responses to current licensed vaccines in order to develop a more effective vaccine that does not rely on annual updates, provides broad protection, and is durable; i.e., a universal influenza vaccine.
The immune response to the influenza vaccine is affected by many parameters, including prior imprinting to a specific influenza strain based on birth cohort, as well as prior influenza vaccination. The FDA-approved, quadrivalent seasonal influenza vaccine that will be administered contains four distinct strains, two influenza A viruses (IAVs) and two influenza B viruses (IBVs). The approved seasonal influenza vaccine will be given for each season of influenza: 2018-2019, 2019-2020, and 2020-2021.
This study is a prospective pilot study conducted over the course of three years (with three specific influenza seasons studied). For each year (2018-2019, 2019-2020, and 2020-2021), two cohorts of 10 participants each, who are in good health and meet all eligibility criteria, will be recruited. The influenza A virus subtype H3N2 cohort (N=30 total, 10 per year) will consist of participants born between 1968-1977, and the influenza A virus subtype H1N1 cohort (N=30 total, 10 per year) will consist of participants born between 1948-1957. Each participant will make a total of six visits to the Hope Clinic. Day 1 will include the informed consent process, and screening to ensure the subject meets all inclusion criteria and meets no exclusion criteria. For the consenting and eligible subject, the visit will also include pre-vaccination phlebotomy for baseline immunogenicity laboratory assays. After baseline sample collection, the participants will receive the FDA-approved seasonal influenza vaccine. Subsequent study visits up to 180 days post-vaccination will include collection for immunogenicity assays.
This study is not powered to test a formal null hypothesis. Rather, it is a hypothesis-generating investigation that will hopefully lead to larger trials based on the findings. The study will be conducted over the course of three years to increase the total sample population size and to validate the findings over different influenza seasons.
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
Georgia
-
Atlanta, Georgia, United States, 30317
- The Hope Clinic of the Emory Vaccine Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Capable of informed consent and provision of written informed consent before any study procedures.
- Capable of attending all study visits according to the study schedule.
- Males or females born between 1968-1977 or 1948-1957.
- Are in good health, as determined by medical history and targeted physical exam related to this history.
- Oral temperature is less than 38 degrees Celsius.
- Resting pulse rate is between 50 and 100 beats per minute.
- Female subjects of childbearing age must have a negative urine pregnancy test within 24 hours before study vaccination.
- Have received the influenza vaccine at least 3 of the past 5 years or have received the influenza vaccine in 2 or less of the past 5 years.
Exclusion Criteria:
- Have an acute illness within 72 hours before vaccination.
- Have any condition that, in the opinion of the principal investigator, would place the subject at an unacceptable risk of harm or confound the interpretation of the study results.
- Have any acute or chronic medical condition that, in the opinion of the principal investigator, would make vaccination unsafe or interfere with the evaluation of immune response to study vaccination.
- Have a suppressed immune system as a result of illness, immunosuppressive medication, chemotherapy, or radiation therapy within 3 years prior to study vaccination.
- Have known HIV, hepatitis B, or hepatitis C infection.
- Have a known history of autoimmune disease.
- Have taken oral or parenteral corticosteroids of any dose within 30 days before study vaccination.
- Have taken high-dose inhaled corticosteroids within 30 days before study vaccination.
- Have received, or plan to receive, any licensed live vaccine within 30 days, or any licensed inactivated vaccine within 14 days, prior to, or after, study vaccination.
- Have planned receipt of any unlicensed or investigational medications, biologics, or vaccines for the duration of subject study participation.
- Have received immunoglobulin or other blood products, with the exception of Rho D immunoglobulin, within 90 days prior to study vaccination.
- Have donated blood or blood products within 30 days before study vaccination, or within 60 days after study vaccination, or plan to donate blood within 30 days of the last blood draw.
- Have known hypersensitivity or allergy to eggs, egg protein, chicken protein, or other compounds of the study vaccine.
- Have a history of severe reactions following vaccination with influenza virus vaccines.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: BASIC_SCIENCE
- Allocation: NON_RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: H3N2 birth cohort
The H3N2 cohort consists of participants born between 1968-1977.
|
The FDA-approved, quadrivalent seasonal influenza vaccine that will be administered contains four distinct strains, two influenza A viruses and two influenza B viruses.
|
EXPERIMENTAL: H1N1 birth cohort
The H1N1 cohort consists of participants born between 1948-1957.
|
The FDA-approved, quadrivalent seasonal influenza vaccine that will be administered contains four distinct strains, two influenza A viruses and two influenza B viruses.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The Number of Participants Achieving Seroprotection Against Each Strain
Time Frame: 28 days after vaccination
|
Seroprotection against each strain contained in the seasonal quadrivalent influenza vaccine (A/H1N1, A/H3N2, B/Phuket, and B/Colorado) were measured by hemagglutination inhibition (HAI) antibody response.
Seroprotection is defined as a titer of ≥ 40.
|
28 days after vaccination
|
The Number of Participants Achieving Seroconversion Against Each Strain
Time Frame: 28 days after vaccination
|
Seroconversion against each strain contained in the seasonal quadrivalent influenza vaccine was measured by HAI antibody response.
Seroconversion is defined as a four-fold rise in HAI post- compared to pre-vaccination, or a titer of ≥40 if the pre-vaccination titer was <10.
|
28 days after vaccination
|
Geometric Mean Titers (GMTs) of Serum HAI Against Each Strain
Time Frame: 28 days after vaccination
|
The geometric scale is logarithmic.
A geometric mean is calculated by averaging the logarithms of the test values and then converting the mean to a real number.
|
28 days after vaccination
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The Proportion of Participants Achieving Seroprotection or Seroconversion Against Each Strain Measured by Neutralizing Antibody (NAb) Response
Time Frame: 28 days after vaccination
|
Seroprotection/seroconversion against each strain contained in the seasonal quadrivalent influenza vaccine will be measured by neutralizing antibody (NAb) response.
The proportion of subjects achieving seroprotection (titer of ≥ 40) or seroconversion (four-fold rise in NAb post- compared to pre-vaccination, or a titer of ≥40 if the pre-vaccination titer was <10) against each strain will be assessed.
|
28 days after vaccination
|
Geometric Mean Titers (GMTs) of Serum NAb Against Each Strain
Time Frame: 28 days after vaccination
|
The geometric scale is logarithmic.
A geometric mean is calculated by averaging the logarithms of the test values and then converting the mean to a real number.
|
28 days after vaccination
|
The Number of Participants Achieving Seroprotection Against Each Strain
Time Frame: 180 days after vaccination
|
Seroprotection against each strain contained in the seasonal quadrivalent influenza vaccine (A/H1N1, A/H3N2, B/Phuket, and B/Colorado) were measured by hemagglutination inhibition (HAI) antibody response.
Seroprotection is defined as a titer of ≥ 40.
|
180 days after vaccination
|
The Number of Participants Achieving Seroconversion Against Each Strain
Time Frame: 180 days after vaccination
|
Seroconversion against each strain contained in the seasonal quadrivalent influenza vaccine was measured by HAI antibody response.
Seroconversion is defined as a four-fold rise in HAI post- compared to pre-vaccination, or a titer of ≥40 if the pre-vaccination titer was <10.
|
180 days after vaccination
|
Geometric Mean Titers (GMTs) of Serum HAI Against Each Strain
Time Frame: 180 days after vaccination
|
The geometric scale is logarithmic.
A geometric mean is calculated by averaging the logarithms of the test values and then converting the mean to a real number.
|
180 days after vaccination
|
The Proportion of Participants Achieving Seroprotection or Seroconversion Against Each Strain Measured by NAb Response
Time Frame: 180 days after vaccination
|
Seroprotection/seroconversion against each strain contained in the seasonal quadrivalent influenza vaccine will be measured by NAb antibody response.
|
180 days after vaccination
|
Geometric Mean Titers (GMTs) of Serum NAb Against Each Strain
Time Frame: 180 days after vaccination
|
The geometric scale is logarithmic.
A geometric mean is calculated by averaging the logarithms of the test values and then converting the mean to a real number.
|
180 days after vaccination
|
Collaborators and Investigators
Sponsor
Publications and helpful links
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- IRB00106407
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Influenza
-
Novartis VaccinesCompletedInfluenza | Seasonal Influenza | Human Influenza | Influenza Due to Unspecified Influenza VirusBelgium
-
Gamaleya Research Institute of Epidemiology and...CompletedInfluenza A | Influenza A Virus Infection | Influenza Epidemic | Influenza H5N1Russian Federation
-
Vanderbilt University Medical CenterHuman Vaccines ProjectCompletedVaccine Reaction | Influenza | Influenza, Human | Influenza A | Influenza Type B | Influenza A H3N2 | Influenza A H1N1United States
-
National Institute of Allergy and Infectious Diseases...CompletedInfluenza Immunisation | Avian InfluenzaUnited States
-
National Institute of Allergy and Infectious Diseases...Completed
-
National Institute of Allergy and Infectious Diseases...Completed
-
National Institute of Allergy and Infectious Diseases...CompletedInfluenza Immunisation | Avian InfluenzaUnited States
-
National Institute of Allergy and Infectious Diseases...CompletedInfluenza | Influenza Immunisation | Avian InfluenzaUnited States
-
National Institute of Allergy and Infectious Diseases...CompletedInfluenza Immunisation | Avian InfluenzaUnited States
-
National Institute of Allergy and Infectious Diseases...National Institutes of Health (NIH)CompletedInfluenza AUnited States
Clinical Trials on FLUARIX QUADRIVALENT
-
GlaxoSmithKlineCompletedInfluenzaSpain, Czechia, United Kingdom, Poland
-
SeqirusCompletedInfluenza, HumanUnited States, Estonia, Germany
-
Sanofi Pasteur, a Sanofi CompanyTerminatedInfluenza ImmunizationUnited States, Denmark, Poland, Spain
-
GlaxoSmithKlineCompletedInfluenzaCanada, Honduras, Dominican Republic
-
Medigen Vaccine Biologics Corp.Completed
-
SeqirusCompleted
-
Tan Tock Seng HospitalSanofi; A*Star; World Health Organization Collaborating Centre for Reference...Recruiting
-
Green Cross CorporationUnknownInfluenzaKorea, Republic of
-
GlaxoSmithKlineCompletedInfluenzaSpain, Taiwan, Canada, United States, Mexico
-
MedicagoCompletedRNA Virus Infections | Virus Diseases | Respiratory Tract Infections | Respiratory Tract DiseasesUnited States, Canada, Finland, Germany, Thailand