title: Malaria DNA vaccine gp96NTD-CSP elicits both CSP-specific antibody and CD8(+) T cell response.
abstract: 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 gp96NTD-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 gp96NTD-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 gp96NTD-CSP were significantly lower than those in the mice immunized either with gp96NTD, CSP, or gp96NTD-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-γ secreted-CSP-specific CD8(+) T cells were much higher in mice immunized with gp96NTD-CSP than those in the mice immunized either with gp96NTD, CSP, or gp96NTD-SYVPSAEQI. Our results suggest that the malaria DNA vaccine gp96NTD-CSP could induce both humoral and cellular immune responses, which is attributed to the adjuvant effect of gp96NTD and full-length CSP.
authors: Department of Pathogenic Biology, The Third Military Medical University, Chongqing, 400038, People's Republic of China.
authors: Zhangping
authors: Z
authors: Tan
authors: TaoLi
authors: T
authors: Zhou
authors: Hong
authors: H
authors: Zheng
authors: Yan
authors: Y
authors: Ding
authors: Wenyue
authors: W
authors: Xu
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D007111:Immunity, Cellular / Q000187:drug effects; D008288:Malaria / Q000517:prevention & control*; D017780:Malaria Vaccines / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018512:Parasitemia / Q000276:immunology; D010967:Plasmodium yoelii / Q000276:immunology*; D015800:Protozoan Proteins / Q000235:genetics; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology; D022223:Vaccines, Subunit / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D018984:Epitopes, T-Lymphocyte; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D019444:Vaccines, DNA; D022223:Vaccines, Subunit