Safety and immunogenicity of NYVAC-JEV and ALVAC-JEV attenuated recombinant Japanese encephalitis virus - poxvirus vaccines in vaccinia-nonimmune andvaccinia-immune humans

A controlled, randomized, double-blind clinical trial evaluated whether two attenuated recombinant poxviruses with identical Japanese encephalitis vir us (JEV) gene insertions, NYVAC-JEV and ALVAC-JEV, were safe and immunogeni c in volunteers. Groups of 10 volunteers distinguished by vaccinia immune s tatus received two doses of each vaccine. The vaccines appeared to be equal ly safe and well tolerated in volunteers, but more reactogenic than license d formalin-inactivated JE and placebo vaccines given as controls. NYVAC-JEV and ALVAC-JEV vaccine recipients had frequent occurrence of local warmth, erythema, tenderness, and/or arm pain after vaccination. There was no appar ent effect of vaccinia immune status on frequency or magnitude of local and systemic reactions. NYVAC-JEV elicited antibody responses to JEV antigens in recipients but ALVAC-JEV vaccine poorly induced antibody responses. Howe ver, NYVAC-JEV Vaccine induced neutralizing antibody responses only in vacc inia-nonimmune recipients while vaccinia-immune Volunteers failed to develo p protective antibodies (5/5 vs. 0/5 seroconversion, p < 0.01). These data suggest that preexisting immunity to poxvirus vector may suppress antibody responses to recombinant gene products. (C) 2000 Published by Elsevier Scie nce Ltd.