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The Impact of Imprinting and Repeated Influenza Vaccination on Adaptive Immunity, Transcriptomics, and Metabolomics (FLU2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03686514
Recruitment Status : Terminated (The study closed prior to completing year 3 of the study due to the COVID-19 pandemic.)
First Posted : September 27, 2018
Results First Posted : July 13, 2022
Last Update Posted : July 13, 2022
Sponsor:
Information provided by (Responsible Party):
Nadine Rouphael, Emory University

Brief Summary:
The goal of this study is to understand the impact on the human immune system's response to the four strain flu vaccine in individuals who have "imprinted" on specific influenza strains. It will also consider the effects of repeated prior annual influenza vaccination on the immune system.

Condition or disease Intervention/treatment Phase
Influenza Biological: FLUARIX QUADRIVALENT Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 39 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: The Impact of Imprinting and Repeated Influenza Vaccination on Adaptive Immunity, Transcriptomics, and Metabolomics
Actual Study Start Date : October 22, 2018
Actual Primary Completion Date : June 20, 2020
Actual Study Completion Date : June 20, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Flu Flu Shot Vaccines

Arm Intervention/treatment
Experimental: H3N2 birth cohort
The H3N2 cohort consists of participants born between 1968-1977.
Biological: FLUARIX QUADRIVALENT
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.
Biological: FLUARIX QUADRIVALENT
The FDA-approved, quadrivalent seasonal influenza vaccine that will be administered contains four distinct strains, two influenza A viruses and two influenza B viruses.




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   42 Years to 71 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Capable of informed consent and provision of written informed consent before any study procedures.
  2. Capable of attending all study visits according to the study schedule.
  3. Males or females born between 1968-1977 or 1948-1957.
  4. Are in good health, as determined by medical history and targeted physical exam related to this history.
  5. Oral temperature is less than 38 degrees Celsius.
  6. Resting pulse rate is between 50 and 100 beats per minute.
  7. Female subjects of childbearing age must have a negative urine pregnancy test within 24 hours before study vaccination.
  8. 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:

  1. Have an acute illness within 72 hours before vaccination.
  2. 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.
  3. 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.
  4. Have a suppressed immune system as a result of illness, immunosuppressive medication, chemotherapy, or radiation therapy within 3 years prior to study vaccination.
  5. Have known HIV, hepatitis B, or hepatitis C infection.
  6. Have a known history of autoimmune disease.
  7. Have taken oral or parenteral corticosteroids of any dose within 30 days before study vaccination.
  8. Have taken high-dose inhaled corticosteroids within 30 days before study vaccination.
  9. 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.
  10. Have planned receipt of any unlicensed or investigational medications, biologics, or vaccines for the duration of subject study participation.
  11. Have received immunoglobulin or other blood products, with the exception of Rho D immunoglobulin, within 90 days prior to study vaccination.
  12. 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.
  13. Have known hypersensitivity or allergy to eggs, egg protein, chicken protein, or other compounds of the study vaccine.
  14. Have a history of severe reactions following vaccination with influenza virus vaccines.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03686514


Locations
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United States, Georgia
The Hope Clinic of the Emory Vaccine Center
Atlanta, Georgia, United States, 30317
Sponsors and Collaborators
Emory University
Investigators
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Principal Investigator: Nadine Rouphael, MD Emory University
  Study Documents (Full-Text)

Documents provided by Nadine Rouphael, Emory University:
Publications of Results:
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Responsible Party: Nadine Rouphael, Professor, Emory University
ClinicalTrials.gov Identifier: NCT03686514    
Other Study ID Numbers: IRB00106407
First Posted: September 27, 2018    Key Record Dates
Results First Posted: July 13, 2022
Last Update Posted: July 13, 2022
Last Verified: June 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Nadine Rouphael, Emory University:
Flu vaccine
Influenza vaccine
Immune response
Influenza strain
Additional relevant MeSH terms:
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Influenza, Human
Respiratory Tract Infections
Infections
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Diseases