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Development of Childhood Anti-Influenza Immunity

Primary Purpose

Influenza, Influenza Immunisation

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Influenza Virus Quadrivalent Inactivated Vaccine
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Influenza focused on measuring B Cell, CD4 T Cell, Children, Influenza Vaccination, Protective Immunity

Eligibility Criteria

3 Months - 15 Years (Child)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • University of Rochester Medical Center - Strong Memorial Hospital - Infectious Diseases

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Cohort 1A

Cohort 1B

Cohort 2A

Cohort 2B

Cohort 3A

Cohort 3B

Cohort 4A

Cohort 4B

Arm Description

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

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

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

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

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

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

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

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

Outcomes

Primary Outcome Measures

Frequency of CD4 T Cells With a Given Functional Potential
Percent of ICOS/PD1+ expressing cells within CXCR5+ CD4 T cell population

Secondary Outcome Measures

Full Information

First Posted
August 30, 2018
Last Updated
March 17, 2022
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
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1. Study Identification

Unique Protocol Identification Number
NCT03673345
Brief Title
Development of Childhood Anti-Influenza Immunity
Official Title
Effect of Influenza Vaccination or Infection on the Development of Protective Immunity in Children
Study Type
Interventional

2. Study Status

Record Verification Date
March 29, 2021
Overall Recruitment Status
Completed
Study Start Date
September 25, 2018 (Actual)
Primary Completion Date
December 22, 2020 (Actual)
Study Completion Date
December 22, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Influenza, Influenza Immunisation
Keywords
B Cell, CD4 T Cell, Children, Influenza Vaccination, Protective Immunity

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
125 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1A
Arm Type
Experimental
Arm Description
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
Arm Title
Cohort 1B
Arm Type
Experimental
Arm Description
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
Arm Title
Cohort 2A
Arm Type
Experimental
Arm Description
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
Arm Title
Cohort 2B
Arm Type
Experimental
Arm Description
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
Arm Title
Cohort 3A
Arm Type
Experimental
Arm Description
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
Arm Title
Cohort 3B
Arm Type
Experimental
Arm Description
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
Arm Title
Cohort 4A
Arm Type
Experimental
Arm Description
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
Arm Title
Cohort 4B
Arm Type
Experimental
Arm Description
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
Intervention Type
Biological
Intervention Name(s)
Influenza Virus Quadrivalent Inactivated Vaccine
Intervention Description
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).
Primary Outcome Measure Information:
Title
Frequency of CD4 T Cells With a Given Functional Potential
Description
Percent of ICOS/PD1+ expressing cells within CXCR5+ CD4 T cell population
Time Frame
Year 2 (Visit 5)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
3 Months
Maximum Age & Unit of Time
15 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: 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 Gestational age of = / > 37 weeks at birth Parent/Legally Authorized Representative (LAR) can provide informed consent, with children = / > 8 years of age providing informed assent Available for the duration of the study 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 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 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: Immunosuppression as a result of an underlying illness or condition (including the human immunodeficiency virus (HIV) or a primary immunodeficiency syndrome) Active neoplastic disease Use of potentially immunosuppressive medications currently or within the past year (including chemotherapeutic agents) or chronic (> 2 weeks) use of oral corticosteroid therapy A diagnosis of asthma requiring chronic inhaled corticosteriod use 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 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) Receipt of immunoglobulin or another blood product within the year prior to study enrollment An acute illness within the previous 3 days or temperature > 38 degrees Celsius on screening except for participation in the natural infection (B) cohorts. A contraindication to influenza vaccination except infants between 3 and 5 months presenting with natural influenza infection whose only contraindication is their current age. 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) Recent (within 120 days) hospitalization, excluding hospitalization for delivery or subjects enrolled in the acute cohort who have been hospitalized for influenza-related reasons 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
Facility Information:
Facility Name
University of Rochester Medical Center - Strong Memorial Hospital - Infectious Diseases
City
Rochester
State/Province
New York
ZIP/Postal Code
14642-0001
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Development of Childhood Anti-Influenza Immunity

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