Influenza Immunity in Children

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.

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.

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