Comparison of protective efficacies of plasmid DNAs encoding Japanese encephalitis virus proteins that induce neutralizing antibody or cytotoxic T lymphocytes in mice

Mice immunized with a plasmid DNA encoding the premembrane (prM) and envelope (E) proteins of Japanese encephalitis (JE) virus (designated pcJEME) produce neutralizing antibodies and are protected from JE. To determine the role of the immune response to other viral proteins in protection, we constructed plasmid DNAs encoding other JE virus proteins and made a direct comparison among these plasmids using a mouse model. Cytotoxic T lymphocytes (CTLs) were induced by plasmids encoding capsid (C) or nonstructural proteins, NS1, NS2A, NS2B, NS3 or NS5. However, these plasmids provided only a partial protection against intraperitoneal challenge with a lethal dose of JE virus, whereas mice immunized with pcJEME were fully protected. In mice inoculated with CTL-inducing plasmids, high virus titers were detected in plasma immediately (1h) following challenge and in brain on day 4 post-challenge, but no virus infectivity was detected in plasma and brain of pcJEME-immunized mice during the 5 days following challenge. These results indicate that protection provided by the prM/E-encoding DNA consists of neutralizing antibody that prevents virus dissemination from the peripheral site to the brain, and that this antibody-mediated mechanism of protection is more efficient than the immunity induced by plasmids that generate CTL responses capable of killing JE virus-infected cells.