Effect of Age and Prior Immunity to Response to Seasonal Influenza Vaccines in Children

The study will be conducted as a randomized, prospective, open-label evaluation of the
clinical tolerability, vaccine virus shedding, and serum and mucosal antibody response to
vaccination with either live trivalent influenza vaccine (LAIV) or trivalent influenza
vaccine (TIV) in healthy children between the ages of 2 and 9 years. Children will be
screened for antibody to A/Brisbane/57/07 (H1N1) and A/California/07/09 (H1N1),
A/Perth/16/2009 (H3N2) and B/Brisbane/60/2008 before and at indicated times after the start
of the study. They will not be randomized based on antibody levels. Children with prior
documented infection with the 2009 pandemic H1N1 virus will be excluded. Vaccine will be
administered on days 0 and 28.

Safety of vaccination will be assessed using symptoms collected by parents for 7 days after
each dose of vaccine. Serum will be obtained prior to and on day 28 following each dose of
vaccine and assessed for antibody by HAI, ELISA, and neutralization techniques. Nasal
secretions will be obtained by nasal wick prior to and on day 28 after each dose and
assessed for HA-specific IgA and IgG antibody by ELISA. Nasal swabs will be obtained on
days 2, 4, and 7 after each dose of live vaccine and assessed for the presence and magnitude
of vaccine virus shedding of the live attenuated vaccine by rtRT-PCR and TCID50 on MDCK
cells.