INDUCTION OF JAPANESE ENCEPHALITIS VIRUS-SPECIFIC CYTOTOXIC T-LYMPHOCYTES IN HUMANS BY POXVIRUS-BASED JE VACCINE CANDIDATES

Poxvirus-based recombinant Japanese encephalitis (JE) vaccine candidat es, NYVAC-JEV and ALVAC-JEV, were examined for their ability to induce JE virus-specific cytotoxic T lymphocytes (CTLs) in a phase I clinica l trial. These vaccine candidates encoded the JE virus premembrane (pr M), envelope (E) and non-structural 1 (NS1) proteins. The volunteers r eceived subcutaneous inoculations with each of these candidates on day s 0 and 28, and blood was drawn 2 days before vaccination and on day 5 8. Anti-E and anti-NS1 antibodies were elicited in most vaccinees inoc ulated with NYVAC-JEV and in some vaccinees inoculated with ALVAC-JEV. Peripheral blood mononuclear cells (PBMCs) obtained from approximatel y one half of vaccines showed positive proliferation in response to st imulation of live JE virus. Cytotoxic assays demonstrated the presence of JE virus-specific CTLs in in vitro-stimulated PBMCs obtained from two NYVAC-JEV and two ALVAC-JEV vaccinees. Cell depletion tests using PBMCs from one NYVAC-JEV recipient indicated that the phenotype of CTL s was CD8(+)CD4(-). (C) 1998 Elsevier Science Ltd. All rights reserved .