Influenza Immunity in Children
Condition: Influenza
MeSH terms: Influenza, Human
Study type: Interventional

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.
    

Intervention name(s): Seasonal IIV 0.25 mL dose; Natural influenza infection; Seasonal IIV 0.5 mL dose
Intervention type(s): Biological; Other; Biological
Intervention description(s): Fluzone (Sanofi Pasteur) 0.25 mL administered intramuscularly to children between 6 and 35 months of age; Children enrolled on presentation to their primary care provider with a natural influenza infection; Fluzone (Sanofi Pasteur) 0.25 mL administered intramuscularly to children between 6 and 35 months of age
Other intervention name(s): Inactivated influenza vaccine; inactivated influenza vaccine
Intervention MeSH terms: Vaccines
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: natural influenza infection; live attenuated influenza vaccination (LAIV); inactivated influenza vaccination (IIV); infants; children