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PNAS:针对金黄色葡萄球菌的候选预防疫苗

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摘要 : 科研人员报告了一种候选的组合疫苗能为小鼠带来针对金黄色葡萄球菌(Staphylococcus aureus)临床分离株的改善了的保护,金黄色葡萄球菌是具有新出现的抗生素耐药性株型的人类病原体。 开发一种针对金黄色葡萄球菌的有效的预防疫苗被证明具有挑战性,这部分是由于缺乏针对这种病原体的天然免疫的证据,这种病原体制造了几种规避免疫的因子。

科研人员报告了一种候选的组合疫苗能为小鼠带来针对金黄色葡萄球菌(Staphylococcus aureus)临床分离株的改善了的保护,金黄色葡萄球菌是具有新出现的抗生素耐药性株型的人类病原体。

开发一种针对金黄色葡萄球菌的有效的预防疫苗被证明具有挑战性,这部分是由于缺乏针对这种病原体的天然免疫的证据,这种病原体制造了几种规避免疫的因子。

Rino Rappuoli及其同事开发了一种候选疫苗,它是基于金黄色葡萄球菌的5个涉及发病机理的抗原——FhuD2、Csa1A、Hla、EsxA和 EsxB。与明矾佐剂组合起来,这种被命名为4C-Staph的联合疫苗比单个抗原更大程度地减少了接种疫苗的小鼠的细菌载量,这些小鼠之前注射了金黄色葡萄球菌的临床菌株。

此外,与在此前试验中测试的单个抗原疫苗相比,4C-Staph疫苗在病原体诱导的腹膜炎与肺炎小鼠模型中提供了针对具有遗传差异的菌株的更好的保护。把接种了4C-Staph的兔的血清注射给之前注射了金黄色葡萄球菌的小鼠,能减少细菌载量并且提改善生存,这表明了这种疫苗的被动免疫保护性抗体的作用。

把这种疫苗与针对TLR7受体的免疫激活模块结合起来,能增强这种疫苗的有效性,增强保护性抗体的水平,触发一种独特的辅助性t细胞应答,并且改善接触致命剂量的金黄色葡萄球菌的小鼠的存活。

这组作者说,有效的佐剂与细胞调控的免疫可能对于金黄色葡萄球菌预防性疫苗的成功具有关键作用。

原文链接:

Vaccine composition formulated with a novel TLR7-dependent adjuvant induces high and broad protection against Staphylococcus aureus doi:10.1073/pnas.1424924112

Both active and passive immunization strategies against Staphylococcus aureus have thus far failed to show efficacy in humans. With the attempt to develop an effective S. aureus vaccine, we selected five conserved antigens known to have different roles in S. aureus pathogenesis. They include the secreted factors α-hemolysin (Hla), ess extracellular A (EsxA), and ess extracellular B (EsxB) and the two surface proteins ferric hydroxamate uptake D2 and conserved staphylococcal antigen 1A. The combined vaccine antigens formulated with aluminum hydroxide induced antibodies with opsonophagocytic and functional activities and provided consistent protection in four mouse models when challenged with a panel of epidemiologically relevant S. aureus strains. The importance of antibodies in protection was demonstrated by passive transfer experiments. Furthermore, when formulated with a toll-like receptor 7-dependent (TLR7) agonist recently designed and developed in our laboratories (SMIP.7–10) adsorbed to alum, the five antigens provided close to 100% protection against four different staphylococcal strains. The new formulation induced not only high antibody titers but also a Th1 skewed immune response as judged by antibody isotype and cytokine profiles. In addition, low frequencies of IL-17–secreting T cells were also observed. Altogether, our data demonstrate that the rational selection of mixtures of conserved antigens combined with Th1/Th17 adjuvants can lead to promising vaccine formulations against S. aureus.

作者:Fabio Bagnoli 点击:

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