Characterization of Pb51 in Plasmodium berghei as a malaria vaccine candidate targeting both asexual erythrocytic proliferation and transmission.
Characterization of Pb51 in Plasmodium berghei as a malaria vaccine candidate targeting both asexual erythrocytic proliferation and transmission.
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伯氏疟原虫中 Pb51 作为针对无性红细胞增殖和传播的候选疟疾疫苗的表征
DOI：
10.1186/s12936-017-2107-2
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发表时间：
2017-11-13
期刊：
影响因子：
3
通讯作者：
Cui L
中科院分区：
文献类型：
--
作者：
Wang J;Zheng W;Liu F;Wang Y;He Y;Zheng L;Fan Q;Luo E;Cao Y;Cui L
针对疟原虫多个发育阶段的疫苗将是控制和消除疟疾的有效工具。通过使用表达和蛋白定位标准的组合搜索PlasmoDB数据库，鉴定了疟原虫中的保守基因，即编码51 kDa蛋白（pb 51基因）的伯氏疟原虫基因（PBANKA_020570）。在原核表达系统（rPb 51）中表达Pb 51蛋白的部分结构域，并用于小鼠中的免疫。Western blot和间接免疫荧光法（IFA）分别检测蛋白表达谱和定位。在体内红细胞中评价抗rPb 51抗体对寄生虫增殖的抑制作用。通过体外动合子转化试验和直接蚊虫取食试验（DFA）测定免疫血清的传播阻断活性。rPb 51在小鼠中引发特异性抗体。Western blot证实Pb 51在胚胎、配子母细胞和动合子中表达。IFA显示Pb ~（51）定位于伯氏疟原虫配子母细胞、合子、受精卵、动合子和子孢子的外膜上。用rPb 51蛋白免疫的小鼠显著降低体内寄生虫增殖和配子体转化。此外，rPb 51抗血清在加入到动合子培养基中时也显著降低了体外动合子转化。在DFA中，用rPb 51免疫的小鼠使蚊子感染率降低21.3%，卵囊密度降低54.8%。在伯氏疟原虫中，P51在无性红细胞期和有性期都有表达，并定位于除环期外的这些阶段的表面。抗rPb 51抗体抑制伯氏疟原虫在小鼠中的增殖和寄生虫向蚊子的传播。
A vaccine that targets multiple developmental stages of malaria parasites would be an effective tool for malaria control and elimination. A conserved gene in Plasmodium, the Plasmodium berghei gene (PBANKA_020570) encoding a 51 kDa protein (pb51 gene), was identified through search of the PlasmoDB database using a combination of expression and protein localization criteria. A partial domain of the Pb51 protein was expressed in a prokaryotic expression system (rPb51) and used for immunization in mice. The protein expression profile and localization were studied by Western blot and indirect immunofluorescence assay (IFA), respectively. The inhibitory effect of the anti-rPb51 antibodies on parasite proliferation was evaluated in erythrocytes in vivo. The transmission-blocking activity of the immune sera was determined by in vitro ookinete conversion assay and by direct mosquito feeding assay (DFA). The rPb51 elicited specific antibodies in mice. Western blot confirmed Pb51 expression in schizonts, gametocytes and ookinetes. IFA showed localization of Pb51 on the outer membranes of schizonts, gametocytes, zygotes, retorts, ookinetes and sporozoites of P. berghei. Mice immunized with the rPb51 protein significantly reduced parasite proliferation and gametocyte conversion in vivo. Moreover, the rPb51 antisera also significantly reduced the in vitro ookinete conversion when added into the ookinete culture medium. In DFA, mice immunized with the rPb51 reduced the prevalence of mosquito infection by 21.3% and oocyst density by 54.8%. In P. berghei, P51 was expressed in both asexual erythrocytic and sexual stages and localized on the surface of these stages with the exception of the ring stage. The anti-rPb51 antibodies inhibited both P. berghei proliferation in mice and transmission of the parasite to mosquitoes.
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影响因子：
5.4
作者：
Long CA;Zavala F
通讯作者：
Zavala F
影响因子：
15.8
作者：
malERA Consultative Group on Vaccines
通讯作者：
malERA Consultative Group on Vaccines
影响因子：
15.8
作者：
Alonso PL;Brown G;Arevalo-Herrera M;Binka F;Chitnis C;Collins F;Doumbo OK;Greenwood B;Hall BF;Levine MM;Mendis K;Newman RD;Plowe CV;Rodríguez MH;Sinden R;Slutsker L;Tanner M
通讯作者：
Tanner M
影响因子：
3.7
作者：
Boes A;Spiegel H;Voepel N;Edgue G;Beiss V;Kapelski S;Fendel R;Scheuermayer M;Pradel G;Bolscher JM;Behet MC;Dechering KJ;Hermsen CC;Sauerwein RW;Schillberg S;Reimann A;Fischer R
通讯作者：
Fischer R
影响因子：
158.5
作者：
Abdulla, Salim;Oberholzer, Rolf;Tanner, Marcel
通讯作者：
Tanner, Marcel