Clinical studies were conducted to determine if pre-existing YFV-specific immunity would impact virus replication upon challenge with YFV-17D or chimeric versions of YFV-17D in which the prM (pre-membrane) and envelope (Env) proteins of YFV-17D were replaced with either JEV [32] or DENV2 [31]. These recombinant viruses, ChimeriVax-JE and ChimeriVax-DEN2, were composed of the YFV-17D capsid (C) structural protein and 7 YFV-17D non-structural proteins, but could no longer be neutralized by YFV-17D-specific antibodies. This provided the opportunity to determine the impact of T cell-mediated protection in the absence of a neutralizing antibody response. YFV-17D infection elicits T cells to both structural and nonstructural proteins [23,24] but pre-existing antiviral T cell memory had no measurable impact on the peak or duration of viremia as determined by area-under-the-curve measurements [31,32,34].