Gene gun-based co-immunization of merozoite surface protein-1 cDNA with IL-12 expression plasmid confers protection against lethal Plasmodium yoelii in A/J mice

The carboxyl-terminal region of the merozoite surface protein-1 (MSPI) is a leading candidate for a vaccine against malaria in the erythrocytic stage. In this study, we investigated the utility of interleukin-12 (IL-12) cDNA as an adjuvant for malaria DNA vaccine in a mouse challenge model. We found that co-immunization of expression plasmids encoding a C-terminal 15-kDa fragment of MSPI (MSP1-15) with the IL-12 gene using a gene gun significantly increased the protective immunity against malaria as compared with MSP1-15 DNA immunization alone. Co-immunization of IL-12 DNA potentiated MSP1-15-specific T helper (Th)1-type immune responses as evaluated by in vivo antibody (Ab) responses and in vitro cytokine profiles. After the Plasmodium yoelii challenge, mice immunized with MSP1-15 plus IL-12 DNA showed a higher level of interferon gamma (IFN-gamma) production than did other groups of mice. In vivo neutralization of IFN-gamma or depletion of CD4(+) T cells completely abolished this protective immunity. Macrophages, but not nitric oxide (NO), were found to play an important role in this effector mechanism. The sera from mice in which the infection had been cleared by the vaccination showed strong protection against P. yoelii infection. Thus, in addition to cellular immune responses, Abs against parasites induced in the course of infection are essential for protection against P. yoelii. The results indicate that combined vaccination with DNA encoding antigenic peptides plus IL-12 DNA provides a strategy for improving the prophylactic efficacy of a vaccine for malaria infection. (C) 2002 Elsevier Science Ltd. All rights reserved.