Japanese encephalitis vaccine(Acambis Plc)

We hypothesize that a high CD4+ and CD8+ T cell count will reduce viremia upon challenge with a structurally heterologous virus, and correspondingly result in reduced magnitude of host response to challenge infection.
Primary Objective: To compare, after challenge with a structurally heterologous vaccine, the differences in levels of viremia between healthy adults who received primary vaccination with either YF17D vaccine, chimeric JE-YF17D vaccine, or inactivated JE vaccine.
58 subjects will be randomised into 1 of 2 arms (Arm B1 and Arm B2) in a 1:1 ratio, in a double-blind fashion. Subjects in Arm B1 will receive JE-YF17D vaccine (Imojev, Sanofi Pasteur) on Day 0 followed by YF17D vaccine (Stamaril, Sanofi Pasteur) on Day 28. Subjects in Arm B2 will receive Stamaril on Day 0 followed by Imojev on Day 28. Arm B3 will be conducted as a separate single-arm open label design in 14 subjects. Subjects in Arm B3 will receive inactivated JE vaccine (Ixiaro, Valneva) on Day 0 followed by Stamaril on Day 28.
The rationale for these three study arms is as follows: Arm B1 will show the impact low levels of viremia, and the resultant low levels of virus-specific CD4+ and CD8+ T cells, would have on YF17D infection. In contrast, YF17D vaccination in Arm B2 would produce high levels of viremia, and in turn high levels virus-specific T cells, thus likely ameliorating JE-YF17D infection. Arm B3 will serve as the control arm, as vaccination with inactivated JE vaccine would not produce any YF17D-specific T cell response. Notably, the first vaccination in Arms B1 and B2 would also provide the viremia response in the absence of virus-specific T cells, which would serve as a reference point to interpret the outcome of the second vaccination.