Simultaneous immunization with DNA and protein vaccines against Japanese encephalitis or dengue synergistically increases their own abilities to induce neutralizing antibody in mice.

Gene-based and protein-based vaccines are two distinct types of vaccines. In this report, we examined if combined use of DNA and protein vaccines would increase their own abilities to induce neutralizing antibody in murine models for Japanese encephalitis (JE) or dengue type 2 (DEN2). DNA vaccines for JE (pcJEME) or DEN2 (pcD2ME) were inoculated intramuscularly, and protein vaccines consisting of subviral extracellular particles (EPs) containing JE (JEEP) or DEN2 (D2EP) virus antigens were inoculated subcutaneously with Freund's adjuvant. Two immunizations of ICR mice with pcJEME and/or JEEP in the prime-boost protocol indicated that levels of neutralizing antibody induced by the pcJEME prime-JEEP boost vaccination were two to eight-fold higher than those induced by pcJEME alone, but were equivalent to those induced by JEEP alone and slightly higher than those induced by the JEEP prime-pcJEME boost regimen. On the other hand, simultaneous immunization of ICR mice with pcJEME and JEEP provided synergistically higher neutralizing antibody titers than those provided by immunization with either immunogen. Immunization with graded doses of pcJEME and JEEP confirmed the synergism. The synergistic increase in neutralizing antibody titer by simultaneous immunization with DNA and protein vaccines was also shown by immunization with pcD2ME and D2EP in ICR and ddY mice. Both IgG1 and IgG2a antibodies were induced by combined immunization with pcJEME and JEEP.