Malaria DNA vaccine gp96(NTD)-CSP elicits both CSP-specific antibody and CD8(+) T cell response

摘要

It is ideal for the pre-erythrocytic stage subunit vaccine to induce both CSP-specific antibody and CD8(+) T cell response. Here, we designed a novel malaria DNA vaccine gp96(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(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(NTD)-CSP were significantly lower than those in the mice immunized either with gp96(NTD), CSP, or gp96(NTD)-SYVPSAEQI, which was constructed by fusing the CSP-specific CD8(+) 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(+) T cells were much higher in mice immunized with gp96(NTD)-CSP than those in the mice immunized either with gp96(NTD), CSP, or gp96(NTD)-SYVPSAEQI. Our results suggest that the malaria DNA vaccine gp96(NTD)-CSP could induce both humoral and cellular immune responses, which is attributed to the adjuvant effect of gp96(NTD) and full-length CSP.