Influenza Immunity in Children

NCT ID: NCT02559505

Last Updated: 2021-09-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 134 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-10-31
• Study Completion Date: 2020-07-03

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.

Conditions

Influenza

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

6-12 months Seasonal IIV

Children 6 - 12 months of age vaccinated with seasonal IIV

Group Type: EXPERIMENTAL

Seasonal IIV 0.25 mL dose

Intervention Type: BIOLOGICAL

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

3-12 months natural infection

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

Group Type: EXPERIMENTAL

Natural influenza infection

Intervention Type: OTHER

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

Seasonal IIV 0.5 mL dose

Intervention Type: BIOLOGICAL

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

13-35 months Seasonal IIV

Children 13-35 months of age vaccinated with seasonal IIV

Group Type: EXPERIMENTAL

Seasonal IIV 0.25 mL dose

Intervention Type: BIOLOGICAL

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

13-35 months natural infection

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

Group Type: EXPERIMENTAL

Natural influenza infection

Intervention Type: OTHER

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

Seasonal IIV 0.5 mL dose

Intervention Type: BIOLOGICAL

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

3-5 years Seasonal IIV

Children 3-5 years of age vaccinated with seasonal IIV

Group Type: EXPERIMENTAL

Seasonal IIV 0.5 mL dose

Intervention Type: BIOLOGICAL

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

3-5 years natural infection

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

Group Type: EXPERIMENTAL

Natural influenza infection

Intervention Type: OTHER

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

Seasonal IIV 0.5 mL dose

Intervention Type: BIOLOGICAL

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

6-8 years Seasonal IIV

Children 6-8 years of age vaccinated with seasonal IIV

Group Type: EXPERIMENTAL

Seasonal IIV 0.5 mL dose

Intervention Type: BIOLOGICAL

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

6-8 years natural infection

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

Group Type: EXPERIMENTAL

Natural influenza infection

Intervention Type: OTHER

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

Seasonal IIV 0.5 mL dose

Intervention Type: BIOLOGICAL

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

Interventions

Seasonal IIV 0.25 mL dose

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

Intervention Type: BIOLOGICAL

Natural influenza infection

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

Intervention Type: OTHER

Seasonal IIV 0.5 mL dose

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

Intervention Type: BIOLOGICAL

Other Intervention Names

Inactivated influenza vaccine; inactivated influenza vaccine

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

• Minimum Eligible Age: 3 Months
• Maximum Eligible Age: 8 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Rochester

OTHER

Sponsor Role: lead

Responsible Party

Jennifer Nayak

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jennifer L Nayak, MD

Role: PRINCIPAL_INVESTIGATOR

University of Rochester

Locations

University of Rochester

Rochester, New York, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 33074330 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

RSRB00058437

Identifier Type: -

Identifier Source: org_study_id