Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Effect of Influenza Vaccination or Infection on the Development of Protective Immunity in Children

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03673345
Recruitment Status : Recruiting
First Posted : September 17, 2018
Last Update Posted : September 9, 2019
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

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 young children depending on early childhood exposures. The primary objective of this study is to evaluate the relationship between influenza A virus exposure, infection and vaccine history, and CD4 T cell and B cell reactivity in a cohort of young children with well documented influenza exposures.

Condition or disease Intervention/treatment Phase
Influenza Influenza Immunisation Biological: Influenza Virus Quadrivalent Inactivated Vaccine Phase 4

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 young children depending on early childhood exposures. The primary objective of this study is to evaluate the relationship between influenza A virus exposure, infection and vaccine history, and CD4 T cell and B cell reactivity in a cohort of young children with well documented influenza exposures. The secondary objective is to determine the durability and breadth of the CD4 T cell response and evaluate for relationships between response durability and factors such as age and exposure history.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 220 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Effect of Influenza Vaccination or Infection on the Development of Protective Immunity in Children
Actual Study Start Date : September 24, 2018
Estimated Primary Completion Date : March 1, 2021
Estimated Study Completion Date : March 1, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Flu Flu Shot

Arm Intervention/treatment
Experimental: 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
Biological: 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).

Experimental: 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
Biological: 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).

Experimental: 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
Biological: 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).

Experimental: 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
Biological: 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).

Experimental: 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
Biological: 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).

Experimental: 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
Biological: 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).

Experimental: 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
Biological: 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).

Experimental: 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
Biological: 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).




Primary Outcome Measures :
  1. Cellular functional potential of CD4 T cell responses using intracellular cytokine staining [ Time Frame: Through year 3 ]
  2. Specificity of CD4 T cell responses using intracellular cytokine staining [ Time Frame: Through year 3 ]

Secondary Outcome Measures :
  1. Avidity of post-vaccination antibody response due to influence of CD4 T cell response [ Time Frame: Through year 3 ]
  2. Breadth of post-vaccination antibody response due to influence of CD4 T cell response [ Time Frame: Through year 3 ]
  3. Change in cellular functional potential [ Time Frame: 24 days post-vaccination in year 1 through Day 0 in year 3 ]
  4. Change in cellular phenotype [ Time Frame: 24 days post-vaccination in year 1 through Day 0 in year 3 ]
  5. Frequency of influenza-specific memory B cells expressing monoclonal antibodies from cloned variable genes of single cells, as determined by ELISPOT and flow cytometry [ Time Frame: Through year 3 ]
  6. Frequency of influenza-specific plasmablasts expressing monoclonal antibodies from cloned variable genes of single cells, as determined by ELISPOT and flow cytometry [ Time Frame: Through year 3 ]
  7. Humoral immune response as measured by antibody titer determined by microneutralization assay [ Time Frame: Through year 3 ]
  8. Humoral immune response as measured by ELISA for antibody binding to HA or NP proteins [ Time Frame: Through year 3 ]
  9. Humoral immune response as measured by HAI assay [ Time Frame: Through year 3 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   3 Months to 15 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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 age 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 age appropriate weight and clinically stable vital signs as determined by a licensed medical provider.

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 or inhaled steroid therapy.
  4. A diagnosis of asthma requiring chronic controller medication.
  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. History of anemia and/or recent (within 120) hospitalization, excluding delivery and subjects who have been hospitalized for influenza-related reasons.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03673345


Contacts
Layout table for location contacts
Contact: Jennifer Nayak 15852759477 jennifer_nayak@urmc.rochester.edu

Locations
Layout table for location information
United States, New York
University of Rochester Medical Center - Strong Memorial Hospital - Infectious Diseases Recruiting
Rochester, New York, United States, 14642-0001
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)

Layout table for additonal information
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT03673345     History of Changes
Other Study ID Numbers: 18-0009
HHSN272201400005C
First Posted: September 17, 2018    Key Record Dates
Last Update Posted: September 9, 2019
Last Verified: September 4, 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
B Cell
Children
Influenza
T Cell
Vaccination
Additional relevant MeSH terms:
Layout table for MeSH terms
Influenza, Human
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases
Vaccines
Immunologic Factors
Physiological Effects of Drugs