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Influenza Immunity in Children

Primary Purpose

Influenza

Status

Completed

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Seasonal IIV 0.25 mL dose

Natural influenza infection

Seasonal IIV 0.5 mL dose

About this trial

This is an interventional basic science trial for Influenza focused on measuring natural influenza infection, live attenuated influenza vaccination (LAIV), inactivated influenza vaccination (IIV), infants, children

Eligibility Criteria

3 Months - 8 Years (Child)All SexesAccepts Healthy Volunteers

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

Sites / Locations

University of Rochester

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm Type

Experimental

Arm Label

6-12 months Seasonal IIV

3-12 months natural infection

13-35 months Seasonal IIV

13-35 months natural infection

3-5 years Seasonal IIV

3-5 years natural infection

6-8 years Seasonal IIV

6-8 years natural infection

Arm Description

Children 6 - 12 months of age vaccinated with seasonal IIV

Children 3-12 months of age presenting with natural influenza infection

Children 13-35 months of age vaccinated with seasonal IIV

Children 13-35 months of age presenting with natural influenza infection

Children 3-5 years of age vaccinated with seasonal IIV

Children 3-5 years of age presenting with natural influenza infection

Children 6-8 years of age vaccinated with seasonal IIV

Children 6-8 years of age presenting with natural influenza infection

Outcomes

Primary Outcome Measures

Mean Percent of IFNg+ CD69+ CD4 T Cells Between Acute (H3N2) Infected and Vaccinated Subjects

% H3- and nucleoprotein (NP)-specific CD4 T cells were measured using intracellular cytokine staining

Mean Percent of IFNg+ CD69+ CD4 T Cells Between Acute (H3N2) Infected and Vaccinated Subjects

% H3- and nucleoprotein (NP)-specific CD4 T cells were measured using intracellular cytokine staining

Mean Percent of IFNg+ CD69+ CD4 T Cells Between Acute (H3N2) Infected and Vaccinated Subjects

% H3- and nucleoprotein (NP)-specific CD4 T cells were measured using intracellular cytokine staining

Mean Percent of IFNg+ CD69+ CD4 T Cells Between Acute (H3N2) Infected and Vaccinated Subjects

% H3 protein- and nucleoprotein (NP)-specific CD4 T cells were measured using intracellular cytokine staining

Mean Percent of IFNg+ CD69+ CD4 T Cells Between Acute (H3N2) Infected and Vaccinated Subjects

% H3 Protein- and nucleoprotein (NP)-specific CD4 T cells were measured using intracellular cytokine staining

Secondary Outcome Measures

Mean Change in Percent of IFNg+ CD69+ CD4 T Cells Between Vaccinated Subjects in Different Age Subsets

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.

Mean Change in Percent of IFNg+ CD69+ CD4 T Cells Between Vaccinated Subjects in Different Age Subsets

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.

Full Information

NCT ID

NCT02559505

First Posted

September 18, 2015

Last Updated

August 5, 2021

Sponsor

University of Rochester

1. Study Identification

Unique Protocol Identification Number

NCT02559505

Brief Title

Influenza Immunity in Children

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2021

Overall Recruitment Status

Completed

Study Start Date

October 2015 (Actual)

Primary Completion Date

July 3, 2020 (Actual)

Study Completion Date

July 3, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Rochester

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Influenza

Keywords

natural influenza infection, live attenuated influenza vaccination (LAIV), inactivated influenza vaccination (IIV), infants, children

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

134 (Actual)

8. Arms, Groups, and Interventions

Arm Title

6-12 months Seasonal IIV

Arm Type

Experimental

Arm Description

Children 6 - 12 months of age vaccinated with seasonal IIV

Arm Title

3-12 months natural infection

Arm Type

Experimental

Arm Description

Children 3-12 months of age presenting with natural influenza infection

Arm Title

13-35 months Seasonal IIV

Arm Type

Experimental

Arm Description

Children 13-35 months of age vaccinated with seasonal IIV

Arm Title

13-35 months natural infection

Arm Type

Experimental

Arm Description

Children 13-35 months of age presenting with natural influenza infection

Arm Title

3-5 years Seasonal IIV

Arm Type

Experimental

Arm Description

Children 3-5 years of age vaccinated with seasonal IIV

Arm Title

3-5 years natural infection

Arm Type

Experimental

Arm Description

Children 3-5 years of age presenting with natural influenza infection

Arm Title

6-8 years Seasonal IIV

Arm Type

Experimental

Arm Description

Children 6-8 years of age vaccinated with seasonal IIV

Arm Title

6-8 years natural infection

Arm Type

Experimental

Arm Description

Children 6-8 years of age presenting with natural influenza infection

Intervention Type

Biological

Intervention Name(s)

Seasonal IIV 0.25 mL dose

Other Intervention Name(s)

Inactivated influenza vaccine

Intervention Description

Fluzone (Sanofi Pasteur) 0.25 mL administered intramuscularly to children between 6 and 35 months of age

Intervention Type

Other

Intervention Name(s)

Natural influenza infection

Intervention Description

Children enrolled on presentation to their primary care provider with a natural influenza infection

Intervention Type

Biological

Intervention Name(s)

Seasonal IIV 0.5 mL dose

Other Intervention Name(s)

inactivated influenza vaccine

Intervention Description

Fluzone (Sanofi Pasteur) 0.25 mL administered intramuscularly to children between 6 and 35 months of age

Primary Outcome Measure Information:

Title

Mean Percent of IFNg+ CD69+ CD4 T Cells Between Acute (H3N2) Infected and Vaccinated Subjects

Description

% H3- and nucleoprotein (NP)-specific CD4 T cells were measured using intracellular cytokine staining

Time Frame

Visit 2 (day 8-14 post enrollment)

Title

Mean Percent of IFNg+ CD69+ CD4 T Cells Between Acute (H3N2) Infected and Vaccinated Subjects

Description

% H3- and nucleoprotein (NP)-specific CD4 T cells were measured using intracellular cytokine staining

Time Frame

Visit 3 (day 20-28 post enrollment)

Title

Mean Percent of IFNg+ CD69+ CD4 T Cells Between Acute (H3N2) Infected and Vaccinated Subjects

Description

% H3- and nucleoprotein (NP)-specific CD4 T cells were measured using intracellular cytokine staining

Time Frame

Visit 4 (day of vaccination year 2)

Title

Mean Percent of IFNg+ CD69+ CD4 T Cells Between Acute (H3N2) Infected and Vaccinated Subjects

Description

% H3 protein- and nucleoprotein (NP)-specific CD4 T cells were measured using intracellular cytokine staining

Time Frame

Visit 5 (day 8-14 post-vaccination year 2)

Title

Mean Percent of IFNg+ CD69+ CD4 T Cells Between Acute (H3N2) Infected and Vaccinated Subjects

Description

% H3 Protein- and nucleoprotein (NP)-specific CD4 T cells were measured using intracellular cytokine staining

Time Frame

Visit 6 (day 20-28 post-vaccination year 2)

Secondary Outcome Measure Information:

Title

Mean Change in Percent of IFNg+ CD69+ CD4 T Cells Between Vaccinated Subjects in Different Age Subsets

Description

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.

Time Frame

Baseline to day 24 study year 1

Title

Mean Change in Percent of IFNg+ CD69+ CD4 T Cells Between Vaccinated Subjects in Different Age Subsets

Description

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.

Time Frame

Baseline to day 24 study year 2

Other Pre-specified Outcome Measures:

Title

Change From Baseline to Day 10 and Day 24 in PBMC Gene Expression

Description

Changes in PBMC gene expression patterns due to prior influenza exposure will be assessed using RNA-seq analysis

Time Frame

Days 10 and 24 post vaccination

10. Eligibility

Sex

All

Minimum Age & Unit of Time

3 Months

Maximum Age & Unit of Time

8 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jennifer L Nayak, MD

Organizational Affiliation

University of Rochester

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Rochester

City

Rochester

State/Province

New York

ZIP/Postal Code

14642

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

33074330

Citation

Shannon I, White CL, Yang H, Nayak JL. Differences in Influenza-Specific CD4 T-Cell Mediated Immunity Following Acute Infection Versus Inactivated Vaccination in Children. J Infect Dis. 2021 Jun 15;223(12):2164-2173. doi: 10.1093/infdis/jiaa664.

Results Reference

derived

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Influenza Immunity in Children

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