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Novel malaria transmission-blocking vaccine development using cell-free protein synthesis system

利用无细胞蛋白质合成系统开发新型疟疾传播阻断疫苗

基本信息

批准号：
16017273
负责人：
TSUBOI Takafumi
金额：
$ 9.6万
依托单位：
Ehime University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research on Priority Areas
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16017273/
关键词：
malaria transmission-blocking vaccine cell-free protein synthesis system international exchange Thailand

项目摘要

Although not providing direct protection for vaccinees, vaccines targeting antigens expressed on the surface of the sexual stages of the parasites are considered one promising strategy for malaria control, and these malaria transmission-blocking vaccines (TBV) have received increased attention over the past decade. This blocks parasite developmental cycles within the mosquito midgut, consequently reducing or preventing parasite transmission to other individuals. TBVs are also expected to prevent the spread of escape mutants emerged during the course of anti-malaria drug treatment or other prophylactic vaccines targeting asexual stages of the parasites. Only four candidate molecules of this type of vaccine are studied for their potential to induce protective immunity, to date. Since the genomic sequence of P falciparum was completed in October 2002, we have now free access to the genome data to search for novel vaccine candidates. However, one of the bottlenecks for the vaccine development is the high AT content in exons of P. falciparum, which will considerably inhibit the recombinant protein expression using conventional methods. Our strategy is to express recombinant proteins for the characterization of each protein based on the genome sequences of P. falciparum without using synthetic gene. In order to identify the novel TBV candidates, we selected 190 genes, which are expected to be expressed only in gametocyte stage of P falciparum. These genes were cloned into plasmids and templates were prepared for transcription through PCR-based procedures, followed by high throughput recombinant protein synthesis by wheat germ cell-free system. Using this approach, we succeeded in obtaining 120 recombinant proteins. After the screening of these recombinant proteins to identify novel TBV candidates with transmission-blocking human sera, we have identified 15 novel gametocyte antigens as TBV candidates.

尽管不能为疫苗接种者提供直接保护，但针对寄生虫性阶段表面表达的抗原的疫苗被认为是控制疟疾的一种有前途的策略，并且这些疟疾传播阻断疫苗（TBV）在过去十年中受到了越来越多的关注。这阻止了蚊子中肠内的寄生虫发育周期，从而减少或防止寄生虫传播给其他个体。 TBV 还有望防止在抗疟疾药物治疗或其他针对寄生虫无性阶段的预防性疫苗过程中出现的逃逸突变体的传播。迄今为止，仅研究了此类疫苗的四种候选分子诱导保护性免疫的潜力。自2002年10月完成恶性疟原虫基因组序列以来，我们现在可以免费获取基因组数据来寻找新的候选疫苗。然而，疫苗开发的瓶颈之一是恶性疟原虫外显子中AT含量较高，这将极大地抑制常规方法重组蛋白的表达。我们的策略是根据恶性疟原虫的基因组序列表达重组蛋白，以表征每种蛋白，而不使用合成基因。为了鉴定新的 TBV 候选者，我们选择了 190 个基因，预计这些基因仅在恶性疟原虫配子体阶段表达。这些基因被克隆到质粒中，并通过基于 PCR 的程序制备用于转录的模板，然后通过小麦胚芽无细胞系统进行高通量重组蛋白合成。利用这种方法，我们成功获得了120种重组蛋白。在筛选这些重组蛋白以鉴定具有阻断传播的人血清的新型 TBV 候选物后，我们已鉴定出 15 种新型配子体抗原作为 TBV 候选物。

项目成果

期刊论文数量（38）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Nasal immunization with a malaria transmission-blocking vaccine candidate, Pfs25, induces complete protective immunity in mice against field isolates of Plasmodium falciparum

DOI：
10.1128/iai.73.11.7375-7380.2005
发表时间：
2005-11-01
期刊：
INFECTION AND IMMUNITY
影响因子：
3.1
作者：
Arakawa, T;Komesu, A;Tsuboi, T
通讯作者：
Tsuboi, T

The Plasmodium falciparum clag9 gene encodes a rhoptry protein that is transferred to the host erythrocyte upon invasion

DOI：
10.1111/j.1365-2958.2003.03969.x
发表时间：
2004-04-01
期刊：
MOLECULAR MICROBIOLOGY
影响因子：
3.6
作者：
Ling, IT;Florens, L;Mattei, D
通讯作者：
Mattei, D

Plasmmodium ookinete-secreted proteins secreted through a common micronemal pathwaay are targets of blocking malaria transmission.

通过共同的微线体途径分泌的疟原虫动蛋白分泌蛋白是阻断疟疾传播的目标。

DOI：
发表时间：
2004
期刊：
Journal of Biological Chamistry 279
影响因子：
0
作者：
Toyooka;K.;et al.;Kaneko O;Yano K;Kaneko 0;Yano K;Arakawa T;Sawasaki T;Arakawa T;Sawasaki T;Arakawa T;Kaneko O;Rungruang T;Sattabongkot J;Li F
通讯作者：
Li F

2-Cys peroxiredoxin TPx-1 is involved in gametocyte development in Plasmodium berghei