Influenza
Conditions
Keywords
Vaccination
Brief summary
This is a prospective pilot study designed to suggest differences in the immunologic response to the seasonal influenza vaccine in people with regular vaccination history compared to those vaccinated less regularly. Participants will receive one dose of the Food and Drug Administration (FDA) approved 2016-2017 seasonal influenza vaccine. Immune system data will be collected at standard time points. The duration of the study for each participant will be approximately 1 month.
Detailed description
This is a prospective pilot study in 20 males and non-pregnant females, 20 to 30 years old, inclusive, who are in good health and meet all eligibility criteria. The study is designed to evaluate differences in the immunologic response to the seasonal influenza vaccine in people with regular vaccination history compared to those vaccinated less regularly. Participants will be sorted to either Arm A (Naïve) or Arm B (Experienced) based on their vaccination history. Those vaccinated no more than 2 out of the past 5 years will be in Arm A. Those vaccinated 3 or more out of the past 5 years will be in Arm B. Participants will receive one dose of the Food and Drug Administration (FDA) approved 2016-2017 seasonal influenza vaccine. The duration of the study for each participant will be approximately 1 month. Subjects will return for clinic visits on Days 3, 8, 15, and 29 during the month follow-up period following vaccination. The study has two primary objectives; to evaluate the antibody response to the influenza vaccine in people who are vaccinated regularly and those vaccinated less regularly; the second is to evaluate circulating follicular helper T cells (TFH) in people who are vaccinated regularly and those vaccinated less regularly.
Interventions
BIOLOGICAL2016-2017 Influenza Vaccine
Quadrivalent influenza A/Hemagglutinin Type 1 (H1N1), A/Influenza A virus subtype (A/H3N2) H3N2,and B virus vaccine for Intramuscular (IM) use is a sterile, clear and slightly opalescent suspension administered as a single 0.5 mL intramuscular dose.
Sponsors
Emory University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 30 Years
Healthy volunteers
Yes
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. * 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 115 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 injury 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 any licensed live vaccine within 30 days or any licensed inactivated vaccine within 14 days prior to study vaccination. * Have planned vaccination with any vaccine during the 29-day 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, plan to donate blood at any time during the 29-day duration of subject study participation, or plan to donate blood within 30 days after 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Geometric Mean Serum Hemagglutination Inhibition (HAI) Antibody Titer | Baseline (Day 1), Day 29 | Geometric mean serum HAI antibody titers serum HAI titer will be collected via blood draw. Titer for serum HAI antibodies will be calculated using the geometric mean. Change is defined as the difference in means from Day 1 to Day 29. |
| Change in Mean Level of Circulating Follicular Helper T (TFH) Cells | Up to 15 Days | TFH cells will be collected via blood draw. Change is defined as the difference in the mean levels of cells from baseline, day 8, and day 15. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mean Levels of Plasmablasts | Up to 29 Days | Plasmablasts will be collected via blood draw. Change is defined as the difference in mean levels from baseline to Day 29. |
| Change in Mean Levels of Memory B Cells From Baseline (Day 1) to Day 29 | Baseline (Day 1) and Day 29 | Memory B cells will be collected via blood draw. Change is defined as the difference in mean levels from baseline to Day 29. |
| Change in Mean Levels of Antigen-specific IL-2 Producing CD4+ T Cells | Up to 29 Days | Antigen-specific Interleukin 2 (IL-2) producing cluster of differentiation 4 (CD4)+ T cells will be collected via blood draw. Change is defined as the difference in mean levels from baseline to Day 29. |
| Change in Mean Levels of Antigen-specific Cluster of Differentiation 8 (CD8) + T Cells | Up to 29 Days | CD8+T cells will be collected via blood draw. Change is defined as the difference in mean levels from baseline to Day 29. |
Countries
United States
Participant flow
Recruitment details
Participants for this study were enrolled from 07/01/2016 to 09/30/2016. Clinical study was conducted at Hope Clinic of Emory University.
Participants by arm
| Arm | Count |
|---|---|
| Vaccination Naïve Participants who have received an influenza vaccine in 2 or less of the past 5 years will receive the FDA-approved 2016-2017 influenza vaccine.
2016-2017 Influenza Vaccine: Quadrivalent influenza A/H1N1, A/H3N2, B virus vaccine for intramuscular use is a sterile, clear and slightly opalescent suspension administered as a single 0.5 mL intramuscular dose. | 10 |
| Vaccination Experienced Participants who have received an influenza vaccine at least 3 of the past 5 years will receive the FDA-approved 2016-2017 influenza vaccine.
2016-2017 Influenza Vaccine: Quadrivalent influenza A/H1N1, A/H3N2, B virus vaccine for intramuscular use is a sterile, clear and slightly opalescent suspension administered as a single 0.5 mL intramuscular dose. | 10 |
| Total | 20 |
Baseline characteristics
| Characteristic | Vaccination Naïve | Vaccination Experienced | Total |
|---|---|---|---|
| Age, Continuous | 23.4 years STANDARD_DEVIATION 1.9 | 24.6 years STANDARD_DEVIATION 2.2 | 24.0 years STANDARD_DEVIATION 2.1 |
| BMI | 25.7 kg/m^2 STANDARD_DEVIATION 8 | 22.8 kg/m^2 STANDARD_DEVIATION 2.77 | 24.3 kg/m^2 STANDARD_DEVIATION 5.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 10 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 9 Participants | 14 Participants |
| Region of Enrollment United States | 10 participants | 10 participants | 20 participants |
| Sex: Female, Male Female | 8 Participants | 9 Participants | 17 Participants |
| Sex: Female, Male Male | 2 Participants | 1 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 0 / 10 | 0 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 |
Outcome results
Primary
Change in Geometric Mean Serum Hemagglutination Inhibition (HAI) Antibody Titer
Geometric mean serum HAI antibody titers serum HAI titer will be collected via blood draw. Titer for serum HAI antibodies will be calculated using the geometric mean. Change is defined as the difference in means from Day 1 to Day 29.
Time frame: Baseline (Day 1), Day 29
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vaccination Naïve | Change in Geometric Mean Serum Hemagglutination Inhibition (HAI) Antibody Titer | Day 1 | 23 HAI antibody Titers | Standard Deviation 19.9 |
| Vaccination Naïve | Change in Geometric Mean Serum Hemagglutination Inhibition (HAI) Antibody Titer | Day 29 | 188 HAI antibody Titers | Standard Deviation 191.4 |
| Vaccination Experienced | Change in Geometric Mean Serum Hemagglutination Inhibition (HAI) Antibody Titer | Day 1 | 56.5 HAI antibody Titers | Standard Deviation 95.7 |
| Vaccination Experienced | Change in Geometric Mean Serum Hemagglutination Inhibition (HAI) Antibody Titer | Day 29 | 108 HAI antibody Titers | Standard Deviation 89 |
Primary
Change in Mean Level of Circulating Follicular Helper T (TFH) Cells
TFH cells will be collected via blood draw. Change is defined as the difference in the mean levels of cells from baseline, day 8, and day 15.
Time frame: Up to 15 Days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vaccination Naïve | Change in Mean Level of Circulating Follicular Helper T (TFH) Cells | Day 1 | 1.9 cells/mm^3 | Standard Deviation 1 |
| Vaccination Naïve | Change in Mean Level of Circulating Follicular Helper T (TFH) Cells | Day 8 | 13.8 cells/mm^3 | Standard Deviation 11.4 |
| Vaccination Naïve | Change in Mean Level of Circulating Follicular Helper T (TFH) Cells | Day 15 | 4.1 cells/mm^3 | Standard Deviation 2.3 |
| Vaccination Experienced | Change in Mean Level of Circulating Follicular Helper T (TFH) Cells | Day 1 | 1.4 cells/mm^3 | Standard Deviation 0.8 |
| Vaccination Experienced | Change in Mean Level of Circulating Follicular Helper T (TFH) Cells | Day 8 | 2.96 cells/mm^3 | Standard Deviation 1.8 |
| Vaccination Experienced | Change in Mean Level of Circulating Follicular Helper T (TFH) Cells | Day 15 | 2.5 cells/mm^3 | Standard Deviation 4.1 |
Secondary
Change in Mean Levels of Antigen-specific Cluster of Differentiation 8 (CD8) + T Cells
CD8+T cells will be collected via blood draw. Change is defined as the difference in mean levels from baseline to Day 29.
Time frame: Up to 29 Days
Population: CD8+T cell assays were not collected since the split virus influenza vaccine was not likely to induce any detectable CD8+ T cell responses.
Secondary
Change in Mean Levels of Antigen-specific IL-2 Producing CD4+ T Cells
Antigen-specific Interleukin 2 (IL-2) producing cluster of differentiation 4 (CD4)+ T cells will be collected via blood draw. Change is defined as the difference in mean levels from baseline to Day 29.
Time frame: Up to 29 Days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vaccination Naïve | Change in Mean Levels of Antigen-specific IL-2 Producing CD4+ T Cells | Day 1 | 0.018 cells/mm^3 | Standard Deviation 0.02 |
| Vaccination Naïve | Change in Mean Levels of Antigen-specific IL-2 Producing CD4+ T Cells | Day 29 | 0.013 cells/mm^3 | Standard Deviation 0.097 |
| Vaccination Experienced | Change in Mean Levels of Antigen-specific IL-2 Producing CD4+ T Cells | Day 1 | 0.018 cells/mm^3 | Standard Deviation 0.017 |
| Vaccination Experienced | Change in Mean Levels of Antigen-specific IL-2 Producing CD4+ T Cells | Day 29 | 0.038 cells/mm^3 | Standard Deviation 0.024 |
Secondary
Change in Mean Levels of Memory B Cells From Baseline (Day 1) to Day 29
Memory B cells will be collected via blood draw. Change is defined as the difference in mean levels from baseline to Day 29.
Time frame: Baseline (Day 1) and Day 29
Population: only 9 participant samples were analyzed as 1 sample could not be analyzed
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vaccination Naïve | Change in Mean Levels of Memory B Cells From Baseline (Day 1) to Day 29 | Day 1 | 0.18 cells/mm^3 | Standard Deviation 0.22 |
| Vaccination Naïve | Change in Mean Levels of Memory B Cells From Baseline (Day 1) to Day 29 | Day 29 | 0.71 cells/mm^3 | Standard Deviation 0.77 |
| Vaccination Experienced | Change in Mean Levels of Memory B Cells From Baseline (Day 1) to Day 29 | Day 1 | 0.46 cells/mm^3 | Standard Deviation 0.72 |
| Vaccination Experienced | Change in Mean Levels of Memory B Cells From Baseline (Day 1) to Day 29 | Day 29 | 0.29 cells/mm^3 | Standard Deviation 0.48 |
Secondary
Change in Mean Levels of Plasmablasts
Plasmablasts will be collected via blood draw. Change is defined as the difference in mean levels from baseline to Day 29.
Time frame: Up to 29 Days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vaccination Naïve | Change in Mean Levels of Plasmablasts | Day 15 | 2.3 cells/mm^3 | Standard Deviation 3 |
| Vaccination Naïve | Change in Mean Levels of Plasmablasts | Day 1 | 2.5 cells/mm^3 | Standard Deviation 2.3 |
| Vaccination Naïve | Change in Mean Levels of Plasmablasts | Day 8 | 6.7 cells/mm^3 | Standard Deviation 5.1 |
| Vaccination Experienced | Change in Mean Levels of Plasmablasts | Day 8 | 0.5 cells/mm^3 | Standard Deviation 0.3 |
| Vaccination Experienced | Change in Mean Levels of Plasmablasts | Day 15 | 0.6 cells/mm^3 | Standard Deviation 0.3 |
| Vaccination Experienced | Change in Mean Levels of Plasmablasts | Day 1 | 0.9 cells/mm^3 | Standard Deviation 0.7 |