Japanese Encephalitis DNA Vaccine Candidates Expressing Premembrane and Envelope Genes Induce Virus-Specific Memory B Cells and Long-Lasting Antibodies in Swine

AbstractSwine are an important amplifier of Japanese encephalitis (JE) virus in the paradomestic environment. In this study, two JE DNA vaccine candidates were evaluated for immunogenicity in swine. Both vaccine plasmids encode a cassette consisting of the signal of premembrane (prM), prM, and envelope (E) coding regions of JE virus. One plasmid, designated pcJEME, is based on a commercial vector (pcDNA3), whereas the other plasmid, designated pNJEME, is based on a vector (pNGVL4a) designed to address some of the safety concerns of DNA vaccine use. No differences were detected in the immunogenicity of these two plasmids in mice or swine. Swine immunized with the DNA vaccines at a dose of 100 to 450 μg at an interval of 3 weeks developed neutralizing and hemagglutination-inhibitory (HAI) antibody titers of 1:40 to 1:160 at 1 week after the second immunization. However, swine administered two doses of a commercial JE vaccine (formalin-inactivated virus preparation; JEVAX-A) developed low (1:10) or undetectable antibody responses after their boost. Interestingly, serum antibody titers elicited by DNA vaccines in swine were higher than those detected in mice. Eight days after boosting with viral antigen (JEVAX-A) to detect an anamnestic response, swine immunized two times with the DNA vaccine showed a >100-fold elevation in HAI titer, indicating a strong recall of antibody response. Swine maintained detectable levels of HAI antibody for at least 245 days after two immunizations with a DNA vaccine. These results indicate that these DNA vaccines are able to induce virus-specific memory B cells and long-lasting antibodies in swine, which were of higher levels than those obtained with a commercial formalin-inactivated JE vaccine