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A Vaccine and Monoclonal Antibodies That Enhance Mouse Resistance to Candida albicans Vaginal Infection

机译:增强小鼠对白色念珠菌阴道感染的抗性的疫苗和单克隆抗体

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摘要

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 β-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°C, 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.
机译:我们以前曾报道过,由白色念珠菌脂质体-甘露聚糖复合物组成的疫苗(L-mann)可刺激小鼠产生针对弥散性念珠菌病的保护性抗体。对复合物中β-1,2-甘露三糖具有特异性的免疫球蛋白M(IgM)单克隆抗体(MAb)B6.1可以预防该疾病,而MAb B6则不能。在本研究中,测试了疫苗和单克隆抗体B6.1和B6的抗阴道念珠菌感染的能力,这种感染是通过在假发情期维持的小鼠中通过阴道内(i.vg.)接种酵母细胞而建立的。确定每个阴道中的真菌CFU以评估感染的严重程度。与未免疫的对照组相比,在感染前接种疫苗的小鼠的阴道CFU减少了约62%。 i.vg接受多克隆抗血清的幼稚小鼠(来自接种疫苗的小鼠)。感染前的CFU比对照组少60%。血清保护因子在56°C稳定,但是白色念珠菌细胞吸收了该因子。给小鼠单克隆抗体B6.1i.vg。建立感染后,阴道组织中念珠菌CFU少于给予缓冲液而不是抗体的对照小鼠。感染前腹膜内给予单克隆抗体B6.1和B6保护小鼠,但酵母细胞预吸收的单克隆抗体没有。 MAb B6.1还可预防热带梭菌阴道感染,但MAb B6不能。 MAb B6.1和B6的保护活性似乎是特异性的,因为无关的IgM碳水化合物特异性MAb和无关的IgG蛋白特异性MAb没有保护性。同样,MAb B6.1也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以帮助宿主抵抗念珠菌阴道感染。

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