Influenza, Influenza Immunisation
Conditions
Keywords
B Cell, CD4 T Cell, Children, Influenza Vaccination, Protective Immunity
Brief summary
This study is a prospective surveillance of the immune response to seasonal vaccination in healthy children. The study will enroll a total of approximately 220 subjects. 140 children will be vaccinated with inactivated influenza vaccine (IIV) and will be divided into 4 age cohorts: 20 children between 6-12 months of age, 60 children greater than 12 months of age and born after 2009, 30 children with a birth date between 2006 and 2009, and 30 children with a birth date between 2003 and 2006. 80 children presenting with natural influenza infection prior to receipt of influenza vaccination also will be divided into 4 age cohorts: 20 children between 3-12 months of age, 20 children greater than 12 months of age with a birth date after 2009, 20 children with a birth date between 2006 and 2009, and 20 children with a birth date between 2003 and 2006. Influenza vaccines will be administered using age-appropriate guidelines in all years of the study: Fluzone 0.25 mL administered intramuscularly to children between 6 and 35 months of age and 0.5 mL to children 36 months of age and older. Subjects will be seen at one domestic site and their participation duration is 2 influenza seasons plus 1 optional season. The primary hypothesis being tested in this study is that there will be differences in the specificity, magnitude and functionality of CD4 T cell and B cell reactivity in a cohort of children depending on early childhood exposures. The primary objective of this study is to evaluate the relationship between influenza virus exposure, infection and vaccine history, and CD4 T cell reactivity in a cohort of children with well documented influenza exposures.
Detailed description
This study is a prospective surveillance of the immune response to seasonal vaccination in healthy children. The study will enroll a total of approximately 220 subjects. 140 children will be vaccinated with inactivated influenza vaccine (IIV) and will be divided into 4 age cohorts: 20 children between 6-12 months of age, 60 children greater than 12 months of age and born after 2009, 30 children with a birth date between 2006 and 2009, and 30 children with a birth date between 2003 and 2006. 80 children presenting with natural influenza infection prior to receipt of influenza vaccination also will be divided into 4 age cohorts: 20 children between 3-12 months of age, 20 children greater than 12 months of age with a birth date after 2009, 20 children with a birth date between 2006 and 2009, and 20 children with a birth date between 2003 and 2006. Influenza vaccines will be administered using age-appropriate guidelines in all years of the study: Fluzone 0.25 mL administered intramuscularly to children between 6 and 35 months of age and 0.5 mL to children 36 months of age and older. Subjects will be seen at one domestic site and their participation duration is 2 influenza seasons plus 1 optional season. The primary hypothesis being tested in this study is that there will be differences in the specificity, magnitude and functionality of CD4 T cell and B cell reactivity in a cohort of children depending on early childhood exposures. The primary objective of this study is to evaluate the relationship between influenza virus exposure, infection and vaccine history, and CD4 T cell reactivity in a cohort of children with well documented influenza exposures.
Interventions
A seasonal quadrivalent inactivated influenza vaccine (IIV4), prepared from influenza viruses propagated in embryonated chicken eggs, protecting against 2 influenza A subtypes (H1N1 and H3N3) and 2 influenza B subtypes (B Yamata lineage B Victoria lineage).
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Months to 15 Years
Healthy volunteers
Yes
Inclusion criteria
1. Age: * Between 6 and 12 months at the time of enrollment to participate in the vaccination arm of age cohort 1A * Between 3 and 12 months at the time of enrollment to participate in the natural infection arm of age cohort 1B * \> 12 months, birth date after 2009 for either the vaccination (A) or natural infection (B) arm of age cohort 2 * Birth date between 2006 and 2009 for either the vaccination (A) or natural infection (B) arm of age cohort 3 * Birth date between 2003 and 2006 for the vaccination (A) or natural infection (B) arm of age cohort 4 2. Gestational age of = / \> 37 weeks at birth 3. Parent/Legally Authorized Representative (LAR) can provide informed consent, with children = / \> 8 years of age providing informed assent 4. Available for the duration of the study 5. History of previous primary inactivated influenza vaccine (IIV) vaccination (at least 2 previous doses for age \< 9 yrs, at least 1 previous dose for age 9 and older) only for participation in the vaccination (A) arm of age cohorts 2, 3, or 4 6. Acute illness documented by rapid influenza test, polymerase chain reaction (PCR) testing, or testing done by either University of Rochester Medical Center (URMC) Labs or Rochester General Hospital (RGH) Clinical Microbiology Labs to be due to influenza virus only for participation in the natural infection arms (B) of age cohorts 1-4 7. Children enrolled in the cohort A (vaccination cohort) are required to have an appropriate weight and vital signs as determined by a licensed medical provider. Children enrolled in the cohort B (natural infection cohort) are required to have an appropriate weight and clinically stable vital signs as determined by a licensed medical provider\* \*Children will not qualify for study participation if their weight is more than 2.5 standard deviations below population norms. This will be determined through calculation of a Z score using the PediTools website (https://www.peditools.org/) utilizing the appropriate Centers for Disease Control and Prevention (CDC) growth calculators for age
Exclusion criteria
1. Immunosuppression as a result of an underlying illness or condition (including the human immunodeficiency virus (HIV) or a primary immunodeficiency syndrome) 2. Active neoplastic disease 3. Use of potentially immunosuppressive medications currently or within the past year (including chemotherapeutic agents) or chronic (\> 2 weeks) use of oral corticosteroid therapy 4. A diagnosis of asthma requiring chronic inhaled corticosteriod use 5. Participation in any clinical research study evaluating an investigational drug or therapy that is inconsistent with current standard of care within two (2) months of enrollment in this study 6. Previous administration of influenza vaccine in the current influenza season only for subjects in the vaccination arm (A) of the study (subjects presenting with acute influenza infection with vaccine failure will be eligible to enroll in the B cohorts) 7. Receipt of immunoglobulin or another blood product within the year prior to study enrollment 8. An acute illness within the previous 3 days or temperature \> 38 degrees Celsius on screening except for participation in the natural infection (B) cohorts. 9. A contraindication to influenza vaccination except infants between 3 and 5 months presenting with natural influenza infection whose only contraindication is their current age. 10. Anemia in the previous 6 months (children on iron supplementation with no documentation of abnormal hemoglobin and/or hematocrit for \>6 months will be allowed to participate in the study) 11. Recent (within 120 days) hospitalization, excluding hospitalization for delivery or subjects enrolled in the acute cohort who have been hospitalized for influenza-related reasons 12. Any medical history or other condition that the study Principal Investigator (PI) feels may have a more than a minimal impact on the immune response or may impact safety of the subject
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of CD4 T Cells With a Given Functional Potential | Year 2 (Visit 5) | Percent of ICOS/PD1+ expressing cells within CXCR5+ CD4 T cell population |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1A 0.25 mL dose of IIV-4 administered intramuscularly on days 0 and 28 of study year 1 and on day 0 of study year 2 in children 6-12 months of age who have not previously had an influenza infection or vaccination, n=20
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 (H1N1 and H3N3) and 2 influenza B subtypes (B Yamata lineage B Victoria lineage). | 5 |
| Cohort 1B 0.25 mL dose of IIV-4 administered intramuscularly on day 0 of study year 2 after primary influenza infection in study year 1 in children 3-12 months of age, who have not previously had an influenza vaccination, n=20
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 (H1N1 and H3N3) and 2 influenza B subtypes (B Yamata lineage B Victoria lineage). | 3 |
| Cohort 2A 0.25 mL (less than 36 months of age) or 0.5 mL (36 months of age or older) dose of IIV-4 administered intramuscularly on day 0 of study year 1 and day 0 of study year 2 in children greater than 12 months of age and born after 2009, who have previously received 2 doses of influenza vaccine prior to the study, n=60
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 (H1N1 and H3N3) and 2 influenza B subtypes (B Yamata lineage B Victoria lineage). | 57 |
| Cohort 2B 0.25 mL (less than 36 months of age) or 0.5 mL (36 months of age or older) dose of IIV-4 administered intramuscularly on day 0 of study year 2 in children greater than 12 months of age and born after 2009, who have previously had an influenza infection in study year 1 and have received 2 doses of influenza vaccine prior to the study, n=20
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 (H1N1 and H3N3) and 2 influenza B subtypes (B Yamata lineage B Victoria lineage). | 12 |
| Cohort 3A 0.5 mL dose of IIV-4 administered intramuscularly on day 0 of study year 1 and day 0 of study year 2 in children born between 2006 and 2009, who have previously received 2 doses of influenza vaccine prior to the study, n=30
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 (H1N1 and H3N3) and 2 influenza B subtypes (B Yamata lineage B Victoria lineage). | 21 |
| Cohort 3B 0.5 mL dose of IIV-4 administered intramuscularly on day 0 of study year 2 in children born between 2006 and 2009, who have previously had an influenza infection in study year 1 and have received 2 doses of influenza vaccine prior to the study, n=20
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 (H1N1 and H3N3) and 2 influenza B subtypes (B Yamata lineage B Victoria lineage). | 7 |
| Cohort 4A 0.5 mL dose of IIV-4 administered intramuscularly on day 0 of study year 1 and day 0 of study year 2 in children born between 2003 and 2006, who have previously received 2 doses of influenza vaccine prior to the study, n=30
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 (H1N1 and H3N3) and 2 influenza B subtypes (B Yamata lineage B Victoria lineage). | 20 |
| Cohort 4B 0.5 mL does of IIV-4 administered intramuscularly on day 0 of study year 2 in children born between 2003 and 2006, who have previously had an influenza infection in study year 1 and have received 2 doses of influenza vaccine prior to the study, n=20
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 (H1N1 and H3N3) and 2 influenza B subtypes (B Yamata lineage B Victoria lineage). | 0 |
| Total | 125 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 | 3 | 3 | 2 | 1 | 0 | 0 |
| Overall Study | Physician Decision | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 4 | 2 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Cohort 1A | Cohort 1B | Cohort 2A | Cohort 2B | Cohort 3A | Cohort 3B | Cohort 4A |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 81.4 months STANDARD_DEVIATION 57.2 | 9.7 months STANDARD_DEVIATION 1.6 | 7.2 months STANDARD_DEVIATION 3.9 | 45.7 months STANDARD_DEVIATION 25.7 | 39.5 months STANDARD_DEVIATION 25.2 | 131.5 months STANDARD_DEVIATION 15.3 | 130.9 months STANDARD_DEVIATION 20 | 167.3 months STANDARD_DEVIATION 9.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 14 Participants | 1 Participants | 1 Participants | 7 Participants | 2 Participants | 2 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 110 Participants | 4 Participants | 2 Participants | 49 Participants | 10 Participants | 19 Participants | 6 Participants | 20 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 22 Participants | 2 Participants | 0 Participants | 13 Participants | 5 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 25 Participants | 1 Participants | 0 Participants | 11 Participants | 3 Participants | 8 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 72 Participants | 2 Participants | 2 Participants | 32 Participants | 3 Participants | 11 Participants | 7 Participants | 15 Participants |
| Sex: Female, Male Female | 68 Participants | 4 Participants | 1 Participants | 33 Participants | 6 Participants | 11 Participants | 2 Participants | 11 Participants |
| Sex: Female, Male Male | 57 Participants | 1 Participants | 2 Participants | 24 Participants | 6 Participants | 10 Participants | 5 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 3 | 0 / 57 | 0 / 12 | 0 / 21 | 0 / 7 | 0 / 20 | 0 / 0 |
| other Total, other adverse events | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
Outcome results
Primary
Frequency of CD4 T Cells With a Given Functional Potential
Percent of ICOS/PD1+ expressing cells within CXCR5+ CD4 T cell population
Time frame: Year 2 (Visit 5)
Population: Unable to enroll participants into Cohort 4B
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1A | Frequency of CD4 T Cells With a Given Functional Potential | 0.70 Percentage | Standard Deviation 0.24 |
| Cohort 1B | Frequency of CD4 T Cells With a Given Functional Potential | 0.55 Percentage | Standard Deviation 0.31 |
| Cohort 2A | Frequency of CD4 T Cells With a Given Functional Potential | 0.52 Percentage | Standard Deviation 0.32 |
| Cohort 2B | Frequency of CD4 T Cells With a Given Functional Potential | 0.38 Percentage | Standard Deviation 0.27 |
| Cohort 3A | Frequency of CD4 T Cells With a Given Functional Potential | 0.40 Percentage | Standard Deviation 0.37 |
| Cohort 3B | Frequency of CD4 T Cells With a Given Functional Potential | 0.34 Percentage | Standard Deviation 0.17 |
| Cohort 4A | Frequency of CD4 T Cells With a Given Functional Potential | 0.30 Percentage | Standard Deviation 0.13 |