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

Primary Purpose

Influenza

Status

Terminated

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

FLUARIX QUADRIVALENT

About this trial

This is an interventional basic science trial for Influenza focused on measuring Flu vaccine, Influenza vaccine, Immune response, Influenza strain

Eligibility Criteria

42 Years - 71 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

The Hope Clinic of the Emory Vaccine Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

H3N2 birth cohort

H1N1 birth cohort

Arm Description

The H3N2 cohort consists of participants born between 1968-1977.

The H1N1 cohort consists of participants born between 1948-1957.

Outcomes

Primary Outcome Measures

The Number of Participants Achieving Seroprotection Against Each Strain

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.

The Number of Participants Achieving Seroconversion Against Each Strain

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.

Geometric Mean Titers (GMTs) of Serum HAI Against Each Strain

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

The Proportion of Participants Achieving Seroprotection or Seroconversion Against Each Strain Measured by Neutralizing Antibody (NAb) Response

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.

Geometric Mean Titers (GMTs) of Serum NAb Against Each Strain

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.

The Number of Participants Achieving Seroprotection Against Each Strain

The Number of Participants Achieving Seroconversion Against Each Strain

Geometric Mean Titers (GMTs) of Serum HAI Against Each Strain

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.

The Proportion of Participants Achieving Seroprotection or Seroconversion Against Each Strain Measured by NAb Response

Seroprotection/seroconversion against each strain contained in the seasonal quadrivalent influenza vaccine will be measured by NAb antibody response.

Geometric Mean Titers (GMTs) of Serum NAb Against Each Strain

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.

Full Information

NCT ID

NCT03686514

First Posted

September 25, 2018

Last Updated

June 16, 2022

Sponsor

Emory University

1. Study Identification

Unique Protocol Identification Number

NCT03686514

Brief Title

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

Acronym

FLU2

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2022

Overall Recruitment Status

Terminated

Why Stopped

The study closed prior to completing year 3 of the study due to the COVID-19 pandemic.

Study Start Date

October 22, 2018 (Actual)

Primary Completion Date

June 20, 2020 (Actual)

Study Completion Date

June 20, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Emory University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Influenza

Keywords

Flu vaccine, Influenza vaccine, Immune response, Influenza strain

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

39 (Actual)

8. Arms, Groups, and Interventions

Arm Title

H3N2 birth cohort

Arm Type

Experimental

Arm Description

The H3N2 cohort consists of participants born between 1968-1977.

Arm Title

H1N1 birth cohort

Arm Type

Experimental

Arm Description

The H1N1 cohort consists of participants born between 1948-1957.

Intervention Type

Biological

Intervention Name(s)

FLUARIX QUADRIVALENT

Intervention Description

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 Measure Information:

Title

The Number of Participants Achieving Seroprotection Against Each Strain

Description

Time Frame

28 days after vaccination

Title

The Number of Participants Achieving Seroconversion Against Each Strain

Description

Time Frame

28 days after vaccination

Title

Geometric Mean Titers (GMTs) of Serum HAI Against Each Strain

Description

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.

Time Frame

28 days after vaccination

Secondary Outcome Measure Information:

Title

The Proportion of Participants Achieving Seroprotection or Seroconversion Against Each Strain Measured by Neutralizing Antibody (NAb) Response

Description

Time Frame

28 days after vaccination

Title

Geometric Mean Titers (GMTs) of Serum NAb Against Each Strain

Description

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.

Time Frame

28 days after vaccination

Title

The Number of Participants Achieving Seroprotection Against Each Strain

Description

Time Frame

180 days after vaccination

Title

The Number of Participants Achieving Seroconversion Against Each Strain

Description

Time Frame

180 days after vaccination

Title

Geometric Mean Titers (GMTs) of Serum HAI Against Each Strain

Description

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.

Time Frame

180 days after vaccination

Title

The Proportion of Participants Achieving Seroprotection or Seroconversion Against Each Strain Measured by NAb Response

Description

Seroprotection/seroconversion against each strain contained in the seasonal quadrivalent influenza vaccine will be measured by NAb antibody response.

Time Frame

180 days after vaccination

Title

Geometric Mean Titers (GMTs) of Serum NAb Against Each Strain

Description

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.

Time Frame

180 days after vaccination

10. Eligibility

Sex

All

Minimum Age & Unit of Time

42 Years

Maximum Age & Unit of Time

71 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Nadine Rouphael, MD

Organizational Affiliation

Emory University

Official's Role

Principal Investigator

Facility Information:

Facility Name

The Hope Clinic of the Emory Vaccine Center

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30317

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

33171854

Citation

Sherman AC, Lai L, Bower M, Natrajan MS, Huerta C, Karmali V, Kleinhenz J, Xu Y, Rouphael N, Mulligan MJ. The Effects of Imprinting and Repeated Seasonal Influenza Vaccination on Adaptive Immunity after Influenza Vaccination. Vaccines (Basel). 2020 Nov 7;8(4):663. doi: 10.3390/vaccines8040663.

Results Reference

result

Learn more about this trial

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

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