Development of Childhood Anti-Influenza Immunity
Condition: Influenza; Influenza Immunisation
MeSH terms: Influenza, Human
Intervention: Influenza Virus Quadrivalent Inactivated Vaccine
Intervention description: 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).
Phase: Phase 4
Study type: Interventional
Primary purpose: Prevention
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 125.0
Sex: All
Minimum age: 3 Months
Maximum age: 15 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: B Cell; CD4 T Cell; Children; Influenza Vaccination; Protective Immunity

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

Eligibility 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 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 Centers for Disease Control and
             Prevention (CDC) growth calculators for age

        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 corticosteroid
             therapy

          4. A diagnosis of asthma requiring chronic inhaled corticosteriod use

          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. 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)

         11. Recent (within 120 days) hospitalization, excluding hospitalization for delivery or
             subjects enrolled in the acute cohort who have been hospitalized for influenza-related
             reasons

         12. Any medical history or other condition that the study Principal Investigator (PI)
             feels may have a more than a minimal impact on the immune response or may impact
             safety of the subject