Immune Response to Influenza Vaccine, Influenza A Virus Infection, Influenza B Virus Infection
Conditions
Keywords
Immune response to influenza vaccine, PCR confirmed Influenza A virus, PCR confirmed Influenza B virus
Brief summary
The purpose of this study is to assess the serologic and cell-mediated immune response to licensed live attenuated influenza vaccine (LAIV) and inactivated influenza vaccine (IIV) in children 5-17 years old. The effects of prior infection and or prior season vaccination will be examined. Children will be followed during the influenza season to identify laboratory-confirmed influenza (i.e. vaccine failure).
Detailed description
All children will have baseline blood samples drawn and will then be vaccinated with licensed and approved influenza vaccines. Following the recommendation from the Advisory Committee on Immunization Practices, children 5-8 years old will preferentially receive live attenuated influenza vaccine (LAIV). Children aged 9-17 will be randomized to receive either LAIV or inactivated influenza vaccine (IIV). Children with a medical contraindication to any licensed influenza vaccine will be excluded from the study. The children will have their blood drawn between 2 and 4 times total over the course of two months in order to test their immune response to the vaccine. Between approximately December and April, study participants will be contacted weekly to monitor for any new respiratory illnesses with cough, and if present, nasal and throat swabs will be collected to test for influenza.
Interventions
BIOLOGICALLAIV
Licensed and approved Live Attenuated Influenza Vaccination (LAIV) will be preferentially given to all children aged 5-8 years old as recommended by Advisory Committee on Immunization Practices. A modified randomization scheme in which every other child aged 9-17 years enrolled in the study will be given LAIV will be used. The rest of the children aged 9-17 years old will receive IIV.
BIOLOGICALIIV
A modified randomization scheme in which every other child aged 9-17 years enrolled in the study will be given IIV will be used. The rest of the children 9-17 years old will receive LAIV. \[Note: Although we do not anticipate exhausting the supply of LAIV, should this occur, children aged 5-8 will be offered IIV as it is also approved in this age group and should be used if LAIV is unavailable.\]
Sponsors
Centers for Disease Control and Prevention
University of Wisconsin, Madison
Marshfield Clinic Research Foundation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
5 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Aged 5-17 years for the duration of the study period (Sept 1, 2014-Apr 1, 2015) * Enrolled in either the immune response study or the vaccine effectiveness study conducted at the site in the 2013-14 influenza season * If enrolled in the vaccine effectiveness study the previous season must have either been vaccinated and infected with influenza or unvaccinated and uninfected with influenza
Exclusion criteria
* Children with contraindications to either the quadrivalent live attenuated influenza vaccine or to the trivalent inactivated influenza vaccine will be excluded. * Anyone unwilling or unable to complete all required study activities including informed consent * Subjects who already received the influenza vaccine for the 2014-15 season
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Hemagglutination Inhibition (HI) Titer Response to Vaccine and Circulating Strains of Influenza | Change from Baseline to 28 days |
Secondary
| Measure | Time frame |
|---|---|
| Polymerase Chain Reaction (PCR) Confirmed Influenza Illness | Onset >13 days after vaccination and before April 1, 2015 |
| Antibody Dependent Cellular Cytotoxicity (ADCC) Titers | Change from Baseline to 28 days |
| Ratio Between Immunoglobulin A (IgA):Immunoglobulin G (IgG) | Day 7 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| LAIV 2014-15 Will receive LAIV this year. Includes 5-8 year olds and approximately half of the 9-17 year olds. Prior history includes vaccine failures, vaccinated/uninfected and unvaccinated/uninfected last year. PBMC available for those who were infected last year, all ages.
LAIV: Licensed and approved Live Attenuated Influenza Vaccination (LAIV) will be preferentially given to all children aged 5-8 years old as recommended by Advisory Committee on Immunization Practices. A modified randomization scheme in which every other child aged 9-17 years enrolled in the study will be given LAIV will be used. The rest of the children aged 9-17 years old will receive IIV. | 85 |
| IIV 2014-15 Will receive IIV this year. Includes only 9-17 year olds (unless shortages of LAIV encountered). Prior history includes vaccine failures, vaccinated/uninfected and unvaccinated/uninfected last year. PBMC available for those who were infected last year, only 9-17 year olds.
IIV: A modified randomization scheme in which every other child aged 9-17 years enrolled in the study will be given IIV will be used. The rest of the children 9-17 years old will receive LAIV.
\[Note: Although we do not anticipate exhausting the supply of LAIV, should this occur, children aged 5-8 will be offered IIV as it is also approved in this age group and should be used if LAIV is unavailable.\] | 46 |
| Total | 131 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Insufficient blood draw amount | 7 | 6 |
Baseline characteristics
| Characteristic | LAIV 2014-15 | IIV 2014-15 | Total |
|---|---|---|---|
| Age, Continuous | 10 YEARS STANDARD_DEVIATION 3.2 | 12 YEARS STANDARD_DEVIATION 2.5 | 11 YEARS STANDARD_DEVIATION 3.2 |
| Sex: Female, Male Female | 35 Participants | 21 Participants | 56 Participants |
| Sex: Female, Male Male | 50 Participants | 25 Participants | 75 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 85 | 0 / 46 |
| serious Total, serious adverse events | 0 / 85 | 0 / 46 |
Outcome results
Primary
Hemagglutination Inhibition (HI) Titer Response to Vaccine and Circulating Strains of Influenza
Time frame: Change from Baseline to 28 days
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| LAIV 2014-15 | Hemagglutination Inhibition (HI) Titer Response to Vaccine and Circulating Strains of Influenza | H3N2 Day 28 HI Titer | 99 Titers |
| LAIV 2014-15 | Hemagglutination Inhibition (HI) Titer Response to Vaccine and Circulating Strains of Influenza | H3N2 Baseline HI Titer | 96 Titers |
| IIV 2014-15 | Hemagglutination Inhibition (HI) Titer Response to Vaccine and Circulating Strains of Influenza | H3N2 Day 28 HI Titer | 295 Titers |
| IIV 2014-15 | Hemagglutination Inhibition (HI) Titer Response to Vaccine and Circulating Strains of Influenza | H3N2 Baseline HI Titer | 100 Titers |
Secondary
Antibody Dependent Cellular Cytotoxicity (ADCC) Titers
Time frame: Change from Baseline to 28 days
Population: Fold change in NK cell degranulation
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| LAIV 2014-15 | Antibody Dependent Cellular Cytotoxicity (ADCC) Titers | Fold change in NK cell degranulation to SW antigen | 1.02 Fold change |
| LAIV 2014-15 | Antibody Dependent Cellular Cytotoxicity (ADCC) Titers | Fold change in NK cell degranulation to TX antigen | 1.10 Fold change |
| IIV 2014-15 | Antibody Dependent Cellular Cytotoxicity (ADCC) Titers | Fold change in NK cell degranulation to SW antigen | 0.99 Fold change |
| IIV 2014-15 | Antibody Dependent Cellular Cytotoxicity (ADCC) Titers | Fold change in NK cell degranulation to TX antigen | 0.95 Fold change |
| LAIV-IIV | Antibody Dependent Cellular Cytotoxicity (ADCC) Titers | Fold change in NK cell degranulation to SW antigen | 1.47 Fold change |
| LAIV-IIV | Antibody Dependent Cellular Cytotoxicity (ADCC) Titers | Fold change in NK cell degranulation to TX antigen | 1.39 Fold change |
| LAIV-LAIV | Antibody Dependent Cellular Cytotoxicity (ADCC) Titers | Fold change in NK cell degranulation to SW antigen | 0.86 Fold change |
| LAIV-LAIV | Antibody Dependent Cellular Cytotoxicity (ADCC) Titers | Fold change in NK cell degranulation to TX antigen | 1.01 Fold change |
| Unvax-IIV | Antibody Dependent Cellular Cytotoxicity (ADCC) Titers | Fold change in NK cell degranulation to SW antigen | 1.31 Fold change |
| Unvax-IIV | Antibody Dependent Cellular Cytotoxicity (ADCC) Titers | Fold change in NK cell degranulation to TX antigen | 1.13 Fold change |
| Unvax-LAIV | Antibody Dependent Cellular Cytotoxicity (ADCC) Titers | Fold change in NK cell degranulation to SW antigen | 1.08 Fold change |
| Unvax-LAIV | Antibody Dependent Cellular Cytotoxicity (ADCC) Titers | Fold change in NK cell degranulation to TX antigen | 1.33 Fold change |
Secondary
Polymerase Chain Reaction (PCR) Confirmed Influenza Illness
Time frame: Onset >13 days after vaccination and before April 1, 2015
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LAIV 2014-15 | Polymerase Chain Reaction (PCR) Confirmed Influenza Illness | 13 participants |
| IIV 2014-15 | Polymerase Chain Reaction (PCR) Confirmed Influenza Illness | 5 participants |
Secondary
Ratio Between Immunoglobulin A (IgA):Immunoglobulin G (IgG)
Time frame: Day 7
Population: There were too few samples collected within each group to conduct a reasonable analysis of this outcome. The samples collected are being stored for potential future use.