Influenza, Influenza Immunisation
Conditions
Keywords
B Cell Response, Children, Evaluation, Healthy Adults, Influenza Vaccine
Brief summary
The study will be designed as a prospective surveillance of the immune response to seasonal influenza vaccination in 240 healthy children and adults ages 9 and over. Study duration will be 5 years, with a participant duration of 6 months. Subjects will receive a quadrivalent inactivated influenza vaccine, at a dose of not less than 15 ug of hemagglutinin (HA), by intramuscular injection in open label fashion on day 0. Blood draws will occur at baseline, day 7, 28 and 90. The primary objective of this study is to evaluate the relationship between first influenza A virus exposure (inferred by age), vaccine history, and baseline serum antibody response to seasonal influenza vaccine in healthy adults and children.
Detailed description
The study will be designed as a prospective surveillance of the immune response to seasonal influenza vaccination in 240 healthy children and adults ages 9 and over. Study duration will be 5 years, with a participant duration of 6 months. Subjects will receive a quadrivalent inactivated influenza vaccine, at a dose of not less than 15 ug of hemagglutinin (HA), by intramuscular injection in open label fashion on day 0. Blood draws will occur at baseline, day 7, 28 and 90. The primary hypothesis being tested in this study is that there will be differences in the specificity and magnitude of the HA-specific B cell response depending on the age, previous vaccine history and baseline B cell reactivity. The primary objective of this study is to evaluate the relationship between first influenza A virus exposure (inferred by age), vaccine history, and baseline serum antibody response to seasonal influenza vaccine in healthy adults and children. The secondary objective is to evaluate factors related to failure of vaccine to provide protection against symptomatic influenza and the immune response to infection in vaccinated individuals by prospective surveillance of the vaccine cohort.
Interventions
A seasonal quadrivalent inactivated influenza vaccine (IIV4), prepared from influenza viruses propagated in embryonated chicken eggs, protecting against 2 influenza A subtypes and 2 influenza B subtypes: A/Singapore/GP1908/2015 (H1N1) IVR-180 (an A/Michigan/45/2015 \[H1N1\] pdm09-like virus), A/Singapore/INFIMH-16-0019/2016 (H3N2) IVR-186, B/Maryland/15/2016 NYMC BX-69A, (a B/Colorado/06/2017-like virus), and B/Phuket/3073/2013.
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
9 Years to 99 Years
Healthy volunteers
Yes
Inclusion criteria
1. Aged equal to or greater than 9 years of age and weigh at least 50 pounds 2. The subject must be in good health, as determined by: medical history; and targeted physical examination, when necessary, based on medical history. Stable medical or psychiatric condition is defined as: no recent increase in prescription medication, dose, or frequency of medication in the last 3 months and health outcomes of the specific disease are considered to be within acceptable limits in the last 6 months 3. The subject is able to understand and comply with the planned study procedures, including being available for all study visits 4. The subject/parent has provided informed consent/assent prior to any study procedures 5. Subjects who have not received seasonal flu vaccine for the current year
Exclusion criteria
1. Subject report of known hypersensitivity to allergy to components of the study vaccine or other components of the study vaccine 2. Subject report of known latex allergy 3. Subject report of a history of severe reactions following previous immunization with licensed or unlicensed influenza virus vaccines 4. Subject report of a history of Guillain-Barre syndrome within 6 weeks of receipt of a previous influenza vaccine 5. The subject is a female of childbearing potential who is currently pregnant or breastfeeding or intends to become pregnant during the study period between enrollment and 90 days following receipt of vaccine. Pregnancy will be determined by subject interview. Pregnancy testing is not done in this study since there is no increased risk in pregnancy 6. The subject is immunosuppressed as a result of an underlying illness or treatment with immunosuppressive or cytotoxic drugs, or use of anticancer chemotherapy or radiation therapy within the preceding 36 months 7. The subject has an active neoplastic disease (excluding non-melanoma skin cancer or prostate cancer that is stable in the absence of therapy) or a history of any hematological malignancy. For this criterion, active is defined as having received treatment within the past 5 years 8. Have taken high-dose inhaled corticosteroids within 30 days prior to study vaccination. High-dose defined as per age as using inhaled high dose per reference chart https://www.nhlbi.nih.gov/health-pro/guidelines/current/asthma-guidelines/quick-reference-html#estimated-comparative-daily-doses 9. The subject received immunoglobulin or another blood product within the 3 months prior to enrollment in this study 10. The subject has received an inactivated vaccine within the 2 weeks or a live vaccine within the 4 weeks prior to enrollment in this study or plans to receive another vaccine within the next 28 days after vaccination 11. The subject has an acute or chronic medical condition that, in the opinion of the investigator or appropriate sub-investigator, would render vaccination unsafe or would interfere with the evaluation of responses. These conditions include any acute or chronic medical disease or conditions defined as persisting for 3 months (defined as 90 days) or longer, that would place the subject at an unacceptable risk of injury, render the subject unable to meet the requirements of the protocol, or may interfere with the evaluation of responses of the subject's successful completion of the study 12. Subjects with an active infection or that has an acute illness or an oral temperature greater than 99.9 degrees Fahrenheit (37.7 degrees Celsius) within 3 days prior to enrollment or vaccination. Subjects who had an acute illness that was treated symptoms resolved are eligible to enroll as long as treatment is completed and symptoms resolved \> 3 days prior to enrollment 13. The subject is currently participating or plans to participate in a study that involves an experimental agent (vaccine, drug, biologic, device, blood product, or medication) or has received an experimental agent within 1 month prior to enrollment in this study, or expects to receive another experimental agent during participation in this study, or intends to donate blood during the study period 14. The subject has any condition that would, in the opinion of the site investigator, place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol 15. The subject has a history of alcohol or drug abuse in the 5 years prior to enrollment 16. The subject has a known human immunodeficiency virus, hepatitis B, or hepatitis C infection 17. Subject weighs less than 50 lbs 18. Subject expects to have a medical procedure during the upcoming 8 weeks that estimates blood loss to exceed 400 cc for adults or for children would exceed 3 ml/kg
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Specificity of the Serum Antibody Response by Microneutralization (MN) | Day 28 | A/H1N1/Michigan/45/2015 pdm09 Day 28 Season 2017-18 |
| Serum Antibody Response by Hemagglutination-inhibition (HAI) | Day 90 | A/Hong Kong/4801/2014 (H3N2) Day 90 Season 2017-2018 |
| Serum Antibody Response by Microneutralization (MN) | Day 90 | A/Hong Kong/4801/2014 (H3N2) Day 90 MN Season 2017-2018 |
| Specificity of the Serum Antibody Response by Hemagglutination-inhibition (HAI) | Day 28 | A/H1N1/Michigan/45/2015 pdm09 Day 28 Season 2017-2018 |
| Magnitude of the Serum Antibody Response by Hemagglutination-inhibition (HAI) | Through Day 28 | A/Hong Kong/4801/2014 (H3N2) day 28 Season 2017-2018 |
| Magnitude of the Serum Antibody Response by Microneutralization (MN) | Day 28 | A/Hong Kong/4801/2014 (H3N2) Day 28 MN Season 2017-2018 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Baseline B Cell Reactivity | Baseline | Comparison between groups: subjects who develop symptomatic influenza (Vaccine Failures) vs. subjects who do not |
| Vaccine History (Number and Percentage of Participants to Receive Vaccine) | Baseline | Comparison between groups: subjects who develop symptomatic influenza (Vaccine Failures) vs. subjects who do not |
| Age at Time of First Influenza A Exposure | Baseline | Comparison between groups: subjects who develop symptomatic influenza (Vaccine Failures) vs. subjects who do not |
Countries
United States
Participant flow
Recruitment details
Healthy adults and children ages 9 and over
Participants by arm
| Arm | Count |
|---|---|
| Arm 1 0.5 mL dose of quadrivalent (IIV-4) vaccine administered once intramuscularly, n=240
Influenza Virus Quadrivalent Inactivated Vaccine: A seasonal quadrivalent inactivated influenza vaccine (IIV4), prepared from influenza viruses propagated in embryonated chicken eggs, protecting against 2 influenza A subtypes and 2 influenza B subtypes: A/Singapore/GP1908/2015 (H1N1) IVR-180 (an A/Michigan/45/2015 \[H1N1\] pdm09-like virus), A/Singapore/INFIMH-16-0019/2016 (H3N2) IVR-186, B/Maryland/15/2016 NYMC BX-69A, (a B/Colorado/06/2017-like virus), and B/Phuket/3073/2013.
Influenza Virus Quadrivalent Inactivated Vaccine: A seasonal quadrivalent inactivated influenza vaccine (IIV4), prepared from influenza viruses propagated in embryonated chicken eggs, protecting against 2 influenza A subtypes and 2 influenza B subtypes: A/Singapore/GP1908/2015 (H1N1) IVR-180 (an A/Michigan/45/2015 \[H1N1\] pdm09-like virus), A/Singapore/INFIMH-16-0019/2016 (H3N2) NIB-104, B/Maryland/15/2016 NYMC BX-69A (a B/Colorado/06/2017-like virus), and B/Phuket/3073/2013. | 152 |
| Total | 152 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Early Study Termination due to COVID-19 pandemic | 3 |
| Overall Study | Lost to Follow-up | 4 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Arm 1 |
|---|---|
| Age, Categorical <=18 years | 23 Participants |
| Age, Categorical >=65 years | 20 Participants |
| Age, Categorical Between 18 and 65 years | 109 Participants |
| Age, Continuous | 43 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 13 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 139 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 137 Participants |
| Sex: Female, Male Female | 93 Participants |
| Sex: Female, Male Male | 59 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 152 |
| other Total, other adverse events | 24 / 152 |
| serious Total, serious adverse events | 1 / 152 |
Outcome results
Primary
Magnitude of the Serum Antibody Response by Hemagglutination-inhibition (HAI)
A/Hong Kong/4801/2014 (H3N2) day 28 Season 2017-2018
Time frame: Through Day 28
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 | Magnitude of the Serum Antibody Response by Hemagglutination-inhibition (HAI) | 528 titer | Geometric Coefficient of Variation 1.38 |
Primary
Magnitude of the Serum Antibody Response by Microneutralization (MN)
A/Hong Kong/4801/2014 (H3N2) Day 28 MN Season 2017-2018
Time frame: Day 28
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 | Magnitude of the Serum Antibody Response by Microneutralization (MN) | 806 titer | Geometric Coefficient of Variation 1.21 |
Primary
Serum Antibody Response by Hemagglutination-inhibition (HAI)
A/Hong Kong/4801/2014 (H3N2) Day 90 Season 2017-2018
Time frame: Day 90
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 | Serum Antibody Response by Hemagglutination-inhibition (HAI) | 115 titer | Geometric Coefficient of Variation 3.08 |
Primary
Serum Antibody Response by Microneutralization (MN)
A/Hong Kong/4801/2014 (H3N2) Day 90 MN Season 2017-2018
Time frame: Day 90
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 | Serum Antibody Response by Microneutralization (MN) | 1389 titer | Geometric Coefficient of Variation 1.08 |
Primary
Specificity of the Serum Antibody Response by Hemagglutination-inhibition (HAI)
A/H1N1/Michigan/45/2015 pdm09 Day 28 Season 2017-2018
Time frame: Day 28
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 | Specificity of the Serum Antibody Response by Hemagglutination-inhibition (HAI) | 665 titer | Geometric Coefficient of Variation 1.73 |
Primary
Specificity of the Serum Antibody Response by Microneutralization (MN)
A/H1N1/Michigan/45/2015 pdm09 Day 28 Season 2017-18
Time frame: Day 28
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 | Specificity of the Serum Antibody Response by Microneutralization (MN) | 2281 titer | Geometric Coefficient of Variation 2.86 |
Secondary
Age at Time of First Influenza A Exposure
Comparison between groups: subjects who develop symptomatic influenza (Vaccine Failures) vs. subjects who do not
Time frame: Baseline
Secondary
Baseline B Cell Reactivity
Comparison between groups: subjects who develop symptomatic influenza (Vaccine Failures) vs. subjects who do not
Time frame: Baseline
Secondary
Vaccine History (Number and Percentage of Participants to Receive Vaccine)
Comparison between groups: subjects who develop symptomatic influenza (Vaccine Failures) vs. subjects who do not
Time frame: Baseline