Malaria DNA vaccine gp96.sub.NTD-CSP elicits both CSP-specific antibody and CD8.sup.+ T cell response

It is ideal for the pre-erythrocytic stage subunit vaccine to induce both CSP-specific antibody and CD8.sup.+ T cell response. Here, we designed a novel malaria DNA vaccine gp96.sub.NTD-CSP, which was constructed by fusing the full-length of CSP with the N-terminal domain of gp96 that deleted the endoplasmic reticulum-localized motif KDEL, and investigated its protective efficacy. We found that the fusion protein gp96.sub.NTD-CSP was mainly distributed on the surface of eukaryotic cells after transfection and could be sensed as a "danger signal" by the host immune system. Interestingly, both liver parasite burden and parasitemia in mice immunized with gp96.sub.NTD-CSP were significantly lower than those in the mice immunized either with gp96.sub.NTD, CSP, or gp96.sub.NTD-SYVPSAEQI, which was constructed by fusing the CSP-specific CD8.sup.+ T cell epitope with the N-terminal domain of gp96 deleted with KDEL. Consistently, both the level of CSP-specific antibody and the frequency of IFN-[gamma] secreted-CSP-specific CD8.sup.+ T cells were much higher in mice immunized with gp96.sub.NTD-CSP than those in the mice immunized either with gp96.sub.NTD, CSP, or gp96.sub.NTD-SYVPSAEQI. Our results suggest that the malaria DNA vaccine gp96.sub.NTD-CSP could induce both humoral and cellular immune responses, which is attributed to the adjuvant effect of gp96.sub.NTD and full-length CSP.