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一种增强小鼠对白色念珠菌阴道感染抵抗力的疫苗和单克隆抗体。

A vaccine and monoclonal antibodies that enhance mouse resistance to Candida albicans vaginal infection.

作者信息

Han Y, Morrison R P, Cutler J E

机构信息

Department of Microbiology, Montana State University, Bozeman, Montana 59717-3520, USA.

出版信息

Infect Immun. 1998 Dec;66(12):5771-6. doi: 10.1128/IAI.66.12.5771-5776.1998.

Abstract

We previously reported that a vaccine composed of liposome-mannan complexes of Candida albicans (L-mann) stimulates mice to produce protective antibodies against disseminated candidiasis. An immunoglobulin M (IgM) monoclonal antibody (MAb), B6.1, specific for a beta-1,2-mannotriose in the complexes protects against the disease, whereas MAb B6 does not. In the present study, the vaccine and MAbs B6.1 and B6 were tested for the ability to protect against Candida vaginal infection, established by intravaginal (i.vg.) inoculation of yeast cells in mice maintained in pseudoestrus. Fungal CFU in each vagina was determined to assess the severity of infection. Mice vaccinated before infection developed about 62% fewer vaginal CFU than nonimmunized controls. Naive mice that received polyclonal antiserum (from vaccinated mice) i.vg. before infection had 60% fewer CFU than controls. The serum protective factor was stable at 56 degreesC, but C. albicans cells absorbed this factor. Mice given MAb B6.1 i.vg. after infection was established had fewer Candida CFU in vaginal tissue than control mice given buffer instead of antibody. MAbs B6.1 and B6 given intraperitoneally before infection protected mice, but MAbs preabsorbed with yeast cells did not. MAb B6.1 also protected against C. tropicalis vaginal infection, but MAb B6 did not. The protective activities of MAbs B6.1 and B6 appeared to be specific because an irrelevant IgM carbohydrate-specific MAb and an irrelevant IgG protein-specific MAb were not protective; also, MAb B6.1 did not affect development of vaginal chlamydial infection. These studies show that an appropriate antibody response, or administration of protective antibodies, can help the host to resist Candida vaginal infection.

摘要

我们之前报道过,由白色念珠菌脂质体-甘露聚糖复合物(L-甘露聚糖)组成的疫苗能刺激小鼠产生针对播散性念珠菌病的保护性抗体。一种免疫球蛋白M(IgM)单克隆抗体(MAb)B6.1,对复合物中的β-1,2-甘露三糖具有特异性,可预防该疾病,而单克隆抗体B6则不能。在本研究中,对该疫苗以及单克隆抗体B6.1和B6进行了测试,以评估其对假动情期小鼠经阴道接种酵母细胞所建立的念珠菌阴道感染的预防能力。通过测定每个阴道中的真菌菌落形成单位(CFU)来评估感染的严重程度。感染前接种疫苗的小鼠阴道CFU比未免疫的对照组少约62%。在感染前经阴道给予多克隆抗血清(来自接种疫苗的小鼠)的未免疫小鼠的CFU比对照组少60%。血清保护因子在56℃时稳定,但白色念珠菌细胞可吸收该因子。在感染建立后经阴道给予单克隆抗体B6.1的小鼠阴道组织中的念珠菌CFU比给予缓冲液而非抗体的对照小鼠少。在感染前腹腔注射单克隆抗体B6.1和B6可保护小鼠,但用酵母细胞预先吸收的单克隆抗体则不能。单克隆抗体B6.1也能预防热带念珠菌阴道感染,但单克隆抗体B6则不能。单克隆抗体B6.1和B6的保护活性似乎具有特异性,因为一种不相关的IgM碳水化合物特异性单克隆抗体和一种不相关的IgG蛋白质特异性单克隆抗体没有保护作用;此外,单克隆抗体B6.1不影响阴道衣原体感染的发展。这些研究表明,适当的抗体反应或给予保护性抗体可帮助宿主抵抗念珠菌阴道感染。

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