Development of Childhood Anti-influenza Immunity

Influenza, Human Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03778203
• Other study ID #: RSRB00073020
• Status: Recruiting
• Phase: Phase 4
• Start date: September 25, 2018
• Est. completion date: December 31, 2021

Study information

• Verified date: July 2020
• Source: University of Rochester
• Contact: Jennifer Nayak
• Phone: 585-275-9477
• Email: jennifer_nayak[@]urmc.rochester.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

More information is needed on how children fight off influenza virus, as they are at greater risk for developing severe influenza infection and tend to have weaker responses to influenza vaccination. The purpose of this study is to understand how a child's early exposure to influenza vaccine or infection with influenza virus prepares him or her to combat future infections with this virus. Investigators will learn about how protection develops following an influenza infection or vaccination and the impact this has on future vaccine responses. The information learned may allow us to develop better vaccines against influenza virus in the future.

Description:

Current guidelines recommend yearly influenza vaccination for all children ≥6 months of age; however the effect this has on the evolution of the anti-influenza immune response through childhood and into adulthood is poorly understood. Though far from idea, yearly vaccination is necessary at present due to the ongoing antigenic drift that occurs as viruses continually evolve to evade neutralizing antibody. There is currently much interest in the development of a universal influenza vaccination that would be able to provide protection against both seasonal and potentially pandemic strains of influenza. However, a growing body of evidence suggests that early childhood influenza exposures result in imprinting that profoundly shapes lifelong CD4 T cell and B cell mediated immunity to this virus. An improved understanding of immunity to influenza virus in early childhood is thus needed if a more broadly protective approach to influenza vaccination is to be successful.

There are profound antigenic differences between natural influenza infection, which stimulates vigorous inflammation with abundant intracellular antigen, and inactivated influenza vaccination, which contains predominately the surface glycoproteins (HA and NA) and promotes weak inflammatory signalling. This study will investigate how the context of these different routes of early childhood influenza exposure affect the functional potential of the anti-influenza immune response and determine the consequences this has on subsequent influenza vaccination. This improved knowledge of how early childhood influenza vaccination shapes the establishment of anti-influenza immunologic memory will enable both optimization of current influenza vaccination strategies and development of novel vaccines able to provide highly efficacious universal protection against both seasonal and potentially pandemic influenza strains.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 700
• Est. completion date: December 31, 2021
• Est. primary completion date: December 31, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 3 Months to 15 Years

Eligibility

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/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 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, PCR testing, or testing done by either URMC Labs or 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 CDC growth calculators for age

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

• 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 >38oC 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 PI feels may have a more than a minimal impact on the immune response or may impact the safety of the subject.

Related Conditions & MeSH terms

• Influenza, Human

Intervention

Biological:
• Fluzone 0.25 mL dose
Fluzone (Sanofi Pasteur) 0.25 mL administered intramuscularly
• Fluzone 0.5 mL dose
Fluzone (Sanofi Pasteur) 0.5 mL administered intramuscularly

Other:
• natural influenza infection
Children enrolled on presentation to their primary care provider or emergency department with a natural influenza infection

Locations

Country	Name	City	State
United States	University of Rochester	Rochester	New York

Sponsors (2)

Lead Sponsor	Collaborator
University of Rochester	University of Chicago

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline to day 10 and day 24 in CD4 T cell responses	CD4 T cell quantity and specificity will be measured using intracellular cytokine staining	Baseline to Day 10 and day 24 post vaccination
Secondary	Change from baseline to day 24 in antibody titers	Amount of post-vaccination antibody will be measured by ELISA assay	Baseline and day 24 post-vaccination