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与Als3p相关的用于治疗白色念珠菌感染的疫苗和抗体。

The vaccines and antibodies associated with Als3p for treatment of Candida albicans infections.

作者信息

Sui Xue, Yan Lan, Jiang Yuan-Ying

机构信息

Center for New Drug Research, School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, PR China; Advanced Institute for Medical Sciences, Dalian Medical University, Dalian, Liaoning Province 116044, PR China.

Center for New Drug Research, School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, PR China.

出版信息

Vaccine. 2017 Oct 13;35(43):5786-5793. doi: 10.1016/j.vaccine.2017.08.082. Epub 2017 Sep 11.

Abstract

Candida albicans is the most common fungal microorganism in healthy individuals, as well as the cause of high mortality infections in high-risk hosts such as immunocompromised patients. Antifungal vaccines and monoclonal antibodies useful for active or passive immunizations have recently generated considerable excitement for the treatment of fungal infections. The cell wall proteins of C. albicans, which are crucial for virulence and pathogenicity, are attractive target antigens. Als3p, a member of the C. albicans agglutinin-like sequence (ALS) family, is a hyphal-specific glycophosphatidylinositol cell wall protein that plays a key role in the interaction with host cells. The abundance of Als3p on the hyphal surface makes it an attractive target. For example, the NDV-3 vaccine, targeted at the N-terminus of Als3p, has entered a preparation of Phase 2 clinical trial. The Als3p-specific antibodies include monoclonal antibodies (MAbs) 3-A5, MAb 113, and scFv3. In addition, MAb C7, MAb 3D9.3 and MAb 2G8, which were supposed to be identifying other targets, have also provided good protection by recognizing Als3p. In this review, we summarize the functions of Als3p and highlight the development of the vaccines and the antibodies that are associated, directly or indirectly, with this protein.

摘要

白色念珠菌是健康个体中最常见的真菌微生物,也是免疫功能低下患者等高风险宿主中导致高死亡率感染的病原体。用于主动或被动免疫的抗真菌疫苗和单克隆抗体最近在真菌感染治疗方面引起了极大的关注。白色念珠菌的细胞壁蛋白对其毒力和致病性至关重要,是有吸引力的靶抗原。Als3p是白色念珠菌凝集素样序列(ALS)家族的成员,是一种菌丝特异性糖基磷脂酰肌醇细胞壁蛋白,在与宿主细胞的相互作用中起关键作用。Als3p在菌丝表面的丰度使其成为一个有吸引力的靶点。例如,针对Als3p N端的NDV-3疫苗已进入2期临床试验准备阶段。Als3p特异性抗体包括单克隆抗体(MAb)3-A5、MAb 113和scFv3。此外,原本认为识别其他靶点的MAb C7、MAb 3D9.3和MAb 2G8,通过识别Als3p也提供了良好的保护作用。在本综述中,我们总结了Als3p的功能,并重点介绍了直接或间接与该蛋白相关的疫苗和抗体的开发情况。

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