Influenza, Human Clinical Trial
Official title:
Effect of Influenza Vaccination or Infection on the Development of Protective Immunity in Children
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.
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.
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