Influenza Immunity in Children

August 5, 2021 updated by: Jennifer Nayak, University of Rochester

Understanding How the Initial Encounter With Influenza Virus Poises Children for Protective Immunity

This study evaluates how different methods of early exposure to influenza (natural infection, live attenuated influenza vaccination, inactivated influenza vaccination) initially stimulate immunity and poise the immune system to respond to a future challenge with the inactivated influenza vaccine.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The proposed research addresses the fact that, despite high childhood morbidity from influenza and broad recommendations for vaccination, very little is known about how anti-influenza immunity is shaped by the method of initial exposure. The objective of this research is to understand how CD4 T cell and B cell responses are altered by the method of initial influenza priming, with the long-term goal of determining how a child's initial influenza encounter poises the immune system to respond to subsequent influenza challenges. The investigators central hypothesis is that differences in the mode of influenza antigen exposure in early childhood will generate long lasting, detectable changes in memory CD4 T cell and B cell specificity and function that influence the response to future influenza vaccinations and infections. This hypothesis will be tested by comparing 1) CD4 T cell and 2) antibody responses in cohorts of children initially exposed to influenza through either natural infection or inactivated or live attenuated vaccination. A combination of multiparameter assays will be used to determine the phenotype and functional potential of hemagglutinin (HA)- and nucleoprotein (NP)-specific CD4 T cells. The breadth and avidity of the neutralizing and non-neutralizing antibody responses and its distribution against head and stalk epitopes will also be evaluated. By determining how initial priming shapes the specificity and functional potential of the anti-influenza CD4 T cell and antibody responses, the investigators will gain the knowledge necessary to optimize current influenza vaccination strategies and develop novel influenza vaccines able to provide highly efficacious universal protection against both seasonal and potentially pandemic viral strains.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
134

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • Rochester, New York, United States, 14642
        • University of Rochester

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

3 months to 8 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age

    • Between 6 and 12 months to participate in the vaccination arm of cohort 1 (cohort 1A)
    • Between 3 and 12 months to participate in the natural infection arm of cohort 1 (cohort 1B)
    • Between 13 and 35 months of age to participate in either the vaccination or natural infection arm of cohort 2
    • Between 36 months and 5 years of age to participate in either the vaccination or natural infection arm of cohort 3
    • Between 6 years and 8 years of age to participate in either the vaccination or natural infection arm of cohort 4
  • Gestational age of ≥37 weeks at birth
  • Parent/guardian can provide informed consent
  • Available for the duration of the study
  • History of previous IIV administration ONLY for participation in the vaccination arm of cohorts 2, 3, or 4
  • Acute illness documented to be due to influenza virus ONLY for participation in the natural infection arms of cohorts 1-4

Exclusion Criteria:

  • Immunosuppression as a result of an underlying illness or condition (including 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 or inhaled steroid therapy
  • A diagnosis of asthma requiring chronic controller medication
  • Previous administration of influenza vaccine in the current influenza season ONLY for subjects receiving an influenza vaccination
  • Receipt of immunoglobulin or another blood product within the year prior to study enrollment
  • An acute illness within the previous 3 days or temperature >38o on screening EXCEPT for participation in the natural infection arms of cohorts 1-4
  • A contraindication to influenza vaccination EXCEPT infants between 3 and 5 months presenting with natural influenza infection whose only contraindication is their current age

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 6-12 months Seasonal IIV
Children 6 - 12 months of age vaccinated with seasonal IIV
Biological: Seasonal IIV 0.25 mL dose
Fluzone (Sanofi Pasteur) 0.25 mL administered intramuscularly to children between 6 and 35 months of age
Other Names:
  • Inactivated influenza vaccine
Experimental: 3-12 months natural infection
Children 3-12 months of age presenting with natural influenza infection
Other: Natural influenza infection
Children enrolled on presentation to their primary care provider with a natural influenza infection
Biological: Seasonal IIV 0.5 mL dose
Fluzone (Sanofi Pasteur) 0.25 mL administered intramuscularly to children between 6 and 35 months of age
Other Names:
  • inactivated influenza vaccine
Experimental: 13-35 months Seasonal IIV
Children 13-35 months of age vaccinated with seasonal IIV
Biological: Seasonal IIV 0.25 mL dose
Fluzone (Sanofi Pasteur) 0.25 mL administered intramuscularly to children between 6 and 35 months of age
Other Names:
  • Inactivated influenza vaccine
Experimental: 13-35 months natural infection
Children 13-35 months of age presenting with natural influenza infection
Other: Natural influenza infection
Children enrolled on presentation to their primary care provider with a natural influenza infection
Biological: Seasonal IIV 0.5 mL dose
Fluzone (Sanofi Pasteur) 0.25 mL administered intramuscularly to children between 6 and 35 months of age
Other Names:
  • inactivated influenza vaccine
Experimental: 3-5 years Seasonal IIV
Children 3-5 years of age vaccinated with seasonal IIV
Biological: Seasonal IIV 0.5 mL dose
Fluzone (Sanofi Pasteur) 0.25 mL administered intramuscularly to children between 6 and 35 months of age
Other Names:
  • inactivated influenza vaccine
Experimental: 3-5 years natural infection
Children 3-5 years of age presenting with natural influenza infection
Other: Natural influenza infection
Children enrolled on presentation to their primary care provider with a natural influenza infection
Biological: Seasonal IIV 0.5 mL dose
Fluzone (Sanofi Pasteur) 0.25 mL administered intramuscularly to children between 6 and 35 months of age
Other Names:
  • inactivated influenza vaccine
Experimental: 6-8 years Seasonal IIV
Children 6-8 years of age vaccinated with seasonal IIV
Biological: Seasonal IIV 0.5 mL dose
Fluzone (Sanofi Pasteur) 0.25 mL administered intramuscularly to children between 6 and 35 months of age
Other Names:
  • inactivated influenza vaccine
Experimental: 6-8 years natural infection
Children 6-8 years of age presenting with natural influenza infection
Other: Natural influenza infection
Children enrolled on presentation to their primary care provider with a natural influenza infection
Biological: Seasonal IIV 0.5 mL dose
Fluzone (Sanofi Pasteur) 0.25 mL administered intramuscularly to children between 6 and 35 months of age
Other Names:
  • inactivated influenza vaccine

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Mean Percent of IFNg+ CD69+ CD4 T Cells Between Acute (H3N2) Infected and Vaccinated Subjects
Time Frame: Visit 2 (day 8-14 post enrollment)
% H3- and nucleoprotein (NP)-specific CD4 T cells were measured using intracellular cytokine staining
Visit 2 (day 8-14 post enrollment)
Mean Percent of IFNg+ CD69+ CD4 T Cells Between Acute (H3N2) Infected and Vaccinated Subjects
Time Frame: Visit 3 (day 20-28 post enrollment)
% H3- and nucleoprotein (NP)-specific CD4 T cells were measured using intracellular cytokine staining
Visit 3 (day 20-28 post enrollment)
Mean Percent of IFNg+ CD69+ CD4 T Cells Between Acute (H3N2) Infected and Vaccinated Subjects
Time Frame: Visit 4 (day of vaccination year 2)
% H3- and nucleoprotein (NP)-specific CD4 T cells were measured using intracellular cytokine staining
Visit 4 (day of vaccination year 2)
Mean Percent of IFNg+ CD69+ CD4 T Cells Between Acute (H3N2) Infected and Vaccinated Subjects
Time Frame: Visit 5 (day 8-14 post-vaccination year 2)
% H3 protein- and nucleoprotein (NP)-specific CD4 T cells were measured using intracellular cytokine staining
Visit 5 (day 8-14 post-vaccination year 2)
Mean Percent of IFNg+ CD69+ CD4 T Cells Between Acute (H3N2) Infected and Vaccinated Subjects
Time Frame: Visit 6 (day 20-28 post-vaccination year 2)
% H3 Protein- and nucleoprotein (NP)-specific CD4 T cells were measured using intracellular cytokine staining
Visit 6 (day 20-28 post-vaccination year 2)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Mean Change in Percent of IFNg+ CD69+ CD4 T Cells Between Vaccinated Subjects in Different Age Subsets
Time Frame: Baseline to day 24 study year 1
CD4 T cell quantity and specificity will be measured using intracellular cytokine staining. We report here the mean change in percent of cells reactive to the influenza HA protein and H3 protein.
Baseline to day 24 study year 1
Mean Change in Percent of IFNg+ CD69+ CD4 T Cells Between Vaccinated Subjects in Different Age Subsets
Time Frame: Baseline to day 24 study year 2
CD4 T cell quantity and specificity will be measured using intracellular cytokine staining. We report here the mean change in percent of cells reactive to the influenza HA protein and H3 protein.
Baseline to day 24 study year 2

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change From Baseline to Day 10 and Day 24 in PBMC Gene Expression
Time Frame: Days 10 and 24 post vaccination
Changes in PBMC gene expression patterns due to prior influenza exposure will be assessed using RNA-seq analysis
Days 10 and 24 post vaccination

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Rochester

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Jennifer L Nayak, MD, University of Rochester

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 1, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 3, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 3, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 18, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 22, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 24, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 2, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 5, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • RSRB00058437

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings