Identification and characterization of a new 34 kDa MORN motif-containing sporozoite surface-exposed protein, Cp-P34, unique to Cryptosporidium.
Identification and characterization of a new 34 kDa MORN motif-containing sporozoite surface-exposed protein, Cp-P34, unique to Cryptosporidium.
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DOI：
10.1016/j.ijpara.2021.01.003
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发表时间：
2021-08
影响因子：
4
通讯作者：
Shoemaker CB
中科院分区：
文献类型：
--
作者：
Jaskiewicz JJ;Tremblay JM;Tzipori S;Shoemaker CB
尽管隐孢子虫引起的儿童腹泻对公共卫生有影响，但目前尚无针对这种寄生虫的有效药物和疫苗。确定疫苗靶点的努力集中在寄生虫侵袭阶段表达的关键外部暴露毒力因子上。然而，目前还没有发现单一的表面抗原可以引起显著的保护性免疫反应，因此很可能需要汇集多个免疫靶点。因此，发现隐孢子虫孢子体表面蛋白对于开发多抗原疫苗至关重要。本研究采用一种新的单域骆驼抗体（VHH）选择方法，对细小隐孢子虫孢子体表面表达的免疫原性蛋白进行鉴定。通过这种方法，vhh被鉴定出能够识别两种暴露于孢子体表面的抗原，即先前鉴定的gp900和未被识别的免疫原性蛋白Cp-P34。这种含有多个膜占领和识别连接（MORN）重复序列的Cp-P34抗原存在于脱落的孢子体和寄生虫的细胞内阶段。Cp-P34似乎在寄生虫体内积累，并短暂地出现在孢子体表面，并在痕迹中脱落。在人隐孢子虫和tyzzeri隐孢子虫基因组中发现了相同或几乎相同的Cp-P34同源物。除了保守的MORN基序外，Cp-P34基因与其他原生动物的基因没有明显的同源性，因此似乎是隐孢子虫所特有的。Cp-P34在自然暴露的羊驼中引起免疫反应，值得进一步研究作为潜在的候选疫苗。
Despite the public health impact of childhood diarrhea caused by Cryptosporidium, effective drugs and vaccines against this parasite are unavailable. Efforts to identify vaccine targets have focused on critical externally exposed virulence factors expressed in the parasite’s invasive stages. However, no single surface antigen has yet been found that can elicit a significant protective immune response and it is likely that pooling multiple immune targets will be necessary. Discovery of surface proteins on Cryptosporidium sporozoites is therefore vital to this effort to develop a multi-antigenic vaccine. In this study we applied a novel single-domain camelid antibody (VHH) selection method to identify immunogenic proteins expressed on the surface of Cryptosporidium parvum sporozoites. By this approach, VHHs were identified that recognize two sporozoite surface-exposed antigens, the previously identified gp900 and an unrecognized immunogenic protein, Cp-P34. This Cp-P34 antigen, which contains multiple Membrane Occupation and Recognition Nexus (MORN) repeats, is found in excysted sporozoites as well as in the parasitès intracellular stages. Cp-P34 appears to accumulate inside the parasite and transiently appears on the surface of sporozoites to be shed in trails. Identical or nearly identical orthologs of Cp-P34 are found in the Cryptosporidium hominis and Cryptosporidium tyzzeri genomes. Except for the conserved MORN motifs, the Cp-P34 gene shares no significant homology with genes of other protozoans and thus appears to be unique to Cryptosporidium spp. Cp-P34 elicits immune responses in naturally exposed alpacas and warrants further investigation as a potential vaccine candidate.
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影响因子：
4
作者：
Gubbels MJ;Duraisingh MT
通讯作者：
Duraisingh MT
影响因子：
2.1
作者：
Boulter-Bitzer, Jeanine I.;Lee, Hung;Trevors, Jack T.
通讯作者：
Trevors, Jack T.
影响因子：
4.8
作者：
Baum, J;Richard, D;Cowman, AF
通讯作者：
Cowman, AF
DOI：
10.4269/ajtmh.2012.11-0273
发表时间：
2012-02-01
影响因子：
3.3
作者：
Borad, Anoli J.;Allison, Geneve M.;Ward, Honorine D.
通讯作者：
Ward, Honorine D.
影响因子：
6.4
作者：
Frost, FJ;Tollestrup, K;Kunde, TR
通讯作者：
Kunde, TR