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The study closed prior to completing year 3 of the study due to the COVID-19 pandemic.
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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.
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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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| H3N2 birth cohort | Experimental | The H3N2 cohort consists of participants born between 1968-1977. |
|
| H1N1 birth cohort | Experimental | The H1N1 cohort consists of participants born between 1948-1957. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| FLUARIX QUADRIVALENT | Biological | The FDA-approved, quadrivalent seasonal influenza vaccine that will be administered contains four distinct strains, two influenza A viruses and two influenza B viruses. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 28 days after vaccination |
| 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. | 28 days after vaccination |
| 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. | 28 days after vaccination |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Nadine Rouphael, MD | Emory University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Hope Clinic of the Emory Vaccine Center | Atlanta | Georgia | 30317 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33171854 | Result | 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. |
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Individuals were permitted to participate in multiple years of the study. One individual belonging to the H1N1 Birth Cohort, born between the years of 1948 and 1957, participated in both the 2018-2019 and 2019-2020 vaccine years. Thus, each vaccine year for this cohort had 10 participants, but there were 19 discrete individuals overall.
Participant enrollment began October 22, 2018 and all follow up was complete by June 20, 2020. Participants were enrolled at the Hope Clinic of the Emory Vaccine Center in Atlanta, Georgia, USA.
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| ID | Title | Description |
|---|---|---|
| FG000 | H3N2 Birth Cohort, Born Between 1968 and 1977 | The H3N2 cohort consists of participants who were born between 1968-1977. Participants received the FLUARIX QUADRIVALENT flu vaccine for the 2018-2019 vaccine year or the 2019-2020 vaccine year. The FDA-approved, quadrivalent seasonal influenza vaccine administered contained four distinct strains, two influenza A viruses and two influenza B viruses. |
| FG001 | H1N1 Birth Cohort, Born Between 1948 and 1957 | The H1N1 cohort consists of participants who were born between 1948-1957. Participants received the FLUARIX QUADRIVALENT flu vaccine for the 2018-2019 vaccine year and/or the 2019-2020 vaccine year. The FDA-approved, quadrivalent seasonal influenza vaccine administered contained four distinct strains, two influenza A viruses and two influenza B viruses. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | H3N2 Birth Cohort, Born Between 1968 and 1977 | The H3N2 cohort consists of participants who were born between 1968-1977. Participants received the FLUARIX QUADRIVALENT flu vaccine for the 2018-2019 vaccine year or the 2019-2020 vaccine year. The FDA-approved, quadrivalent seasonal influenza vaccine administered contained four distinct strains, two influenza A viruses and two influenza B viruses |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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 data for the individual in the H1N1 Birth Cohort who participated in both vaccine years is included for each year of participation. | Posted | Count of Participants | Participants | 28 days after vaccination |
|
Information on adverse events was collected beginning during the first study visit when the influenza vaccine was administered through the final study assessment at 180 days post-vaccination.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | H3N2 Birth Cohort, Born Between 1968 and 1977 | The H3N2 cohort consists of participants who were born between 1968-1977. Participants received the FLUARIX QUADRIVALENT flu vaccine for the 2018-2019 vaccine year or the 2019-2020 vaccine year. The FDA-approved, quadrivalent seasonal influenza vaccine administered contained four distinct strains, two influenza A viruses and two influenza B viruses. |
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Due to the COVID-19 pandemic, this study was terminated prior to beginning year 3 of the study.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Nadine Rouphael, MD | Emory University | 404-712-1435 | nroupha@emory.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Sep 13, 2019 | Mar 16, 2022 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D007251 | Influenza, Human |
| ID | Term |
|---|---|
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
| D009976 | Orthomyxoviridae Infections |
| D012327 | RNA Virus Infections |
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| 28 days after vaccination |
| 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. | 28 days after vaccination |
| 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. | 180 days after vaccination |
| 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. | 180 days after vaccination |
| 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. | 180 days after vaccination |
| 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. | 180 days after vaccination |
| 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. | 180 days after vaccination |
| BG001 | H1N1 Birth Cohort, Born Between 1948 and 1957 | The H1N1 cohort consists of participants who were born between 1948-1957. Participants received the FLUARIX QUADRIVALENT flu vaccine for the 2018-2019 vaccine year and/or the 2019-2020 vaccine year. The FDA-approved, quadrivalent seasonal influenza vaccine administered contained four distinct strains, two influenza A viruses and two influenza B viruses. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| OG001 | H1N1 Birth Cohort, Born Between 1948 and 1957 | The H1N1 cohort consists of participants who were born between 1948-1957. Participants received the FLUARIX QUADRIVALENT flu vaccine for the 2018-2019 vaccine year and/or the 2019-2020 vaccine year. The FDA-approved, quadrivalent seasonal influenza vaccine administered contained four distinct strains, two influenza A viruses and two influenza B viruses. |
|
|
| Primary | 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. | The data for the individual in the H1N1 Birth Cohort who participated in both vaccine years is included for each year of participation. | Posted | Count of Participants | Participants | 28 days after vaccination |
|
|
|
| Primary | 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 data for the individual in the H1N1 Birth Cohort who participated in both vaccine years is included for each year of participation. | Posted | Geometric Mean | Standard Deviation | GMTs | 28 days after vaccination |
|
|
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| Secondary | 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. | NAb testing was not performed as all research efforts moved to coronavirus disease 2019 (COVID-19) research. | Posted | 28 days after vaccination |
|
|
| Secondary | 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. | NAb testing was not performed as all research efforts moved to COVID-19 research. | Posted | 28 days after vaccination |
|
|
| Secondary | 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 data for the individual in the H1N1 Birth Cohort who participated in both vaccine years is included for each year of participation. | Posted | Count of Participants | Participants | 180 days after vaccination |
|
|
|
| Secondary | 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. | The data for the individual in the H1N1 Birth Cohort who participated in both vaccine years is included for each year of participation. | Posted | Count of Participants | Participants | 180 days after vaccination |
|
|
|
| Secondary | 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 data for the individual in the H1N1 Birth Cohort who participated in both vaccine years is included for each year of participation. | Posted | Geometric Mean | Standard Deviation | GMTs | 180 days after vaccination |
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|
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| Secondary | 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. | NAb testing was not performed as all research efforts moved to COVID-19 research. | Posted | 180 days after vaccination |
|
|
| Secondary | 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. | NAb testing was not performed as all research efforts moved to COVID-19 research. | Posted | 180 days after vaccination |
|
|
| 0 |
| 20 |
| 0 |
| 20 |
| 0 |
| 20 |
| EG001 | H1N1 Birth Cohort, Born Between 1948 and 1957 | The H1N1 cohort consists of participants who were born between 1948-1957. Participants received the FLUARIX QUADRIVALENT flu vaccine for the 2018-2019 vaccine year and/or the 2019-2020 vaccine year. The FDA-approved, quadrivalent seasonal influenza vaccine administered contained four distinct strains, two influenza A viruses and two influenza B viruses. One individual participated in both vaccine years and is counted only once for adverse event reporting. | 0 | 19 | 0 | 19 | 0 | 19 |
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| D014777 | Virus Diseases |
| D012140 | Respiratory Tract Diseases |
| B/Phuket |
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| B/Colorado |
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| B/Phuket |
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| B/Colorado |
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| B/Phuket |
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| B/Colorado |
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| B/Phuket |
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| B/Colorado |
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| B/Phuket |
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| B/Colorado |
|