Trial Outcomes & Findings for The Impact of Imprinting and Repeated Influenza Vaccination on Adaptive Immunity, Transcriptomics, and Metabolomics (NCT NCT03686514)

Last Updated: 2022-07-13

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE4

Target enrollment

39 participants

Primary outcome timeframe

28 days after vaccination

Results posted on

2022-07-13

Participant Flow

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.

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 milestones

Participant milestones
Measure	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.	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.
Overall Study STARTED	20	19
Overall Study Started 2018-2019 Vaccine Year	10	10
Overall Study Completed 2018-2019 Vaccine Follow up	10	10
Overall Study Started 2019-2020 Vaccine Year	10	10
Overall Study Completed 2019-2020 Vaccine Follow up	10	10
Overall Study COMPLETED	20	19
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	H3N2 Birth Cohort, Born Between 1968 and 1977 n=20 Participants 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	H1N1 Birth Cohort, Born Between 1948 and 1957 n=19 Participants 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.	Total n=39 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	20 Participants n=5 Participants	7 Participants n=7 Participants	27 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	12 Participants n=7 Participants	12 Participants n=5 Participants
Age, Continuous	45.39 years STANDARD_DEVIATION 2.77 • n=5 Participants	66.95 years STANDARD_DEVIATION 2.29 • n=7 Participants	55.89 years STANDARD_DEVIATION 11.20 • n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	11 Participants n=7 Participants	20 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	8 Participants n=7 Participants	19 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	20 Participants n=5 Participants	19 Participants n=7 Participants	39 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	5 Participants n=5 Participants	3 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) White	11 Participants n=5 Participants	16 Participants n=7 Participants	27 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	20 Participants n=5 Participants	19 Participants n=7 Participants	39 Participants n=5 Participants

PRIMARY outcome

Timeframe: 28 days after vaccination

Population: The data for the individual in the H1N1 Birth Cohort who participated in both vaccine years is included for each year of participation.

Outcome measures

Outcome measures
Measure	H3N2 Birth Cohort, Born Between 1968 and 1977 n=20 Participants 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.	H1N1 Birth Cohort, Born Between 1948 and 1957 n=20 Participants 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.
The Number of Participants Achieving Seroprotection Against Each Strain A/H1N1	19 Participants	20 Participants
The Number of Participants Achieving Seroprotection Against Each Strain A/H3N2	20 Participants	17 Participants
The Number of Participants Achieving Seroprotection Against Each Strain B/Phuket	19 Participants	17 Participants
The Number of Participants Achieving Seroprotection Against Each Strain B/Colorado	20 Participants	20 Participants

PRIMARY outcome

Timeframe: 28 days after vaccination

Population: The data for the individual in the H1N1 Birth Cohort who participated in both vaccine years is included for each year of participation.

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.

Outcome measures

Outcome measures
Measure	H3N2 Birth Cohort, Born Between 1968 and 1977 n=20 Participants 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.	H1N1 Birth Cohort, Born Between 1948 and 1957 n=20 Participants 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.
The Number of Participants Achieving Seroconversion Against Each Strain A/H1N1	11 Participants	10 Participants
The Number of Participants Achieving Seroconversion Against Each Strain A/H3N2	12 Participants	10 Participants
The Number of Participants Achieving Seroconversion Against Each Strain B/Phuket	9 Participants	11 Participants
The Number of Participants Achieving Seroconversion Against Each Strain B/Colorado	8 Participants	8 Participants

PRIMARY outcome

Timeframe: 28 days after vaccination

Population: The data for the individual in the H1N1 Birth Cohort who participated in both vaccine years is included for each year of participation.

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.

Outcome measures

Outcome measures
Measure	H3N2 Birth Cohort, Born Between 1968 and 1977 n=20 Participants 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.	H1N1 Birth Cohort, Born Between 1948 and 1957 n=20 Participants 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.
Geometric Mean Titers (GMTs) of Serum HAI Against Each Strain A/H1N1	282.5 GMTs Standard Deviation 301	389 GMTs Standard Deviation 575
Geometric Mean Titers (GMTs) of Serum HAI Against Each Strain A/H3N2	458 GMTs Standard Deviation 564	539 GMTs Standard Deviation 1097
Geometric Mean Titers (GMTs) of Serum HAI Against Each Strain B/Phuket	463 GMTs Standard Deviation 579	200 GMTs Standard Deviation 183
Geometric Mean Titers (GMTs) of Serum HAI Against Each Strain B/Colorado	258 GMTs Standard Deviation 273	180 GMTs Standard Deviation 260

SECONDARY outcome

Timeframe: 28 days after vaccination

Population: NAb testing was not performed as all research efforts moved to coronavirus disease 2019 (COVID-19) research.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 28 days after vaccination

Population: NAb testing was not performed as all research efforts moved to COVID-19 research.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 180 days after vaccination

Population: The data for the individual in the H1N1 Birth Cohort who participated in both vaccine years is included for each year of participation.

Outcome measures

Outcome measures
Measure	H3N2 Birth Cohort, Born Between 1968 and 1977 n=20 Participants 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.	H1N1 Birth Cohort, Born Between 1948 and 1957 n=20 Participants 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.
The Number of Participants Achieving Seroprotection Against Each Strain A/H1N1	18 Participants	17 Participants
The Number of Participants Achieving Seroprotection Against Each Strain A/H3N2	17 Participants	12 Participants
The Number of Participants Achieving Seroprotection Against Each Strain B/Phuket	17 Participants	14 Participants
The Number of Participants Achieving Seroprotection Against Each Strain B/Colorado	18 Participants	20 Participants

SECONDARY outcome

Timeframe: 180 days after vaccination

Population: The data for the individual in the H1N1 Birth Cohort who participated in both vaccine years is included for each year of participation.

Outcome measures

Outcome measures
Measure	H3N2 Birth Cohort, Born Between 1968 and 1977 n=20 Participants 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.	H1N1 Birth Cohort, Born Between 1948 and 1957 n=20 Participants 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.
The Number of Participants Achieving Seroconversion Against Each Strain A/H1N1	7 Participants	7 Participants
The Number of Participants Achieving Seroconversion Against Each Strain A/H3N2	5 Participants	6 Participants
The Number of Participants Achieving Seroconversion Against Each Strain B/Phuket	4 Participants	5 Participants
The Number of Participants Achieving Seroconversion Against Each Strain B/Colorado	3 Participants	7 Participants

SECONDARY outcome

Timeframe: 180 days after vaccination

Population: The data for the individual in the H1N1 Birth Cohort who participated in both vaccine years is included for each year of participation.

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.

Outcome measures

Outcome measures
Measure	H3N2 Birth Cohort, Born Between 1968 and 1977 n=20 Participants 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.	H1N1 Birth Cohort, Born Between 1948 and 1957 n=20 Participants 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.
Geometric Mean Titers (GMTs) of Serum HAI Against Each Strain A/H1N1	151.2 GMTs Standard Deviation 153	197 GMTs Standard Deviation 191
Geometric Mean Titers (GMTs) of Serum HAI Against Each Strain A/H3N2	124 GMTs Standard Deviation 147	185 GMTs Standard Deviation 297
Geometric Mean Titers (GMTs) of Serum HAI Against Each Strain B/Phuket	135 GMTs Standard Deviation 112	114 GMTs Standard Deviation 92
Geometric Mean Titers (GMTs) of Serum HAI Against Each Strain B/Colorado	130 GMTs Standard Deviation 157	98 GMTs Standard Deviation 67

SECONDARY outcome

Timeframe: 180 days after vaccination

Population: NAb testing was not performed as all research efforts moved to COVID-19 research.

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 180 days after vaccination

Population: NAb testing was not performed as all research efforts moved to COVID-19 research.

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.

Outcome measures

Outcome data not reported

Adverse Events

H3N2 Birth Cohort, Born Between 1968 and 1977

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

H1N1 Birth Cohort, Born Between 1948 and 1957

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Nadine Rouphael, MD

Emory University

Phone: 404-712-1435

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place