INFLUENZA IMMUNITY: PROTECTIVE MECHANISMS AGAINST A PANDEMIC RESPIRATORY VIRUS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The fundamental objective of our Stanford Cooperative Center is to use the analysis of vaccine-induced and naturally-acquired influenza A immunity as a model for defining adaptive and innate immune mechanisms and antimicrobial protection of the respiratory tract in children and younger and older adults. Influenza A was chosen as a model system relevant to biodefense because influenza A has the potential to be modified or manipulated genetically to produce a microbial agent of bioterrorism. Furthermore, influenza A causes natural pandemics, which incapacitate a large fraction of the adult population within a short time-frame, and may endanger defense preparedness. In either circumstance, influenza A has many characteristics of microbial agents that could become civilian bioterrorist agents. Our scientific objective is to study the human host response, with the focus on the humoral and cellular immune responses of both children and adults to vaccine-induced influenza A stimulation. We hope to learn how the immune responses to either live, attenuated influenza vaccine or inactivated influenza vaccine compares between adults and children by studying CD4 T-cells, CD8 T-cells, B-cell immunity and natural killer (NK) cell responses to influenza A before and after immunization. In yr 1, we propose to immunize 64 children 5-9 yrs old and 64 adults 19-49 yrs old. They will be randomized to receive one of two licensed products with a 1:1 allocation: either FluMist (live, attenuated flu vaccine) via intranasal spray or Fluzone (inactivated influenza vaccine) via intramuscular (IM) injection. Blood samples for immunogenicity studies will be drawn prior to immunization and one-month post-immunization for immunogenicity assays.