Antibody-mediated protection against Staphylococcus aureus dermonecrosis and sepsis by a whole cell vaccine.
Antibody-mediated protection against Staphylococcus aureus dermonecrosis and sepsis by a whole cell vaccine.
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全细胞疫苗针对金黄色葡萄球菌皮肤坏死和败血症的抗体介导保护。
DOI：
10.1016/j.vaccine.2017.05.085
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发表时间：
2017
期刊：
影响因子：
5.5
通讯作者：
Lu,Ying-Jie
中科院分区：
文献类型：
--
作者：
Zhang,Fan;Jun,Maria;Ledue,Olivia;Herd,Muriel;Malley,Richard;Lu,Ying-Jie
金黄色葡萄球菌是一种非常重要的人类病原体，在世界范围内引起显著的发病率和死亡率。一些基于产生针对葡萄球菌表面多糖或蛋白质的抗体的疫苗临床试验已经失败。用溶葡萄球菌蛋白裂解一株usa300菌株，然后超声和上清部分的收获，制备了全细胞杀伤裂解物（SaWCA）。用SaWCA和霍乱毒素（CT）免疫产生强大的IL-17A，但相对温和的抗体反应，并在皮肤脓肿中提供保护，但在皮肤坏死或侵袭性感染模型中没有。相比之下，用SaWCA和明矾进行肠外免疫可以产生强大的抗体和IL-17A反应，并在所有三种模型中保护小鼠。用SaWCA免疫后产生的血清具有可测量的针对6种被测保守表面蛋白的抗体，并提高了针对2种os的调理吞噬活性（OPA）。aureusstrains。被动转移sawca免疫血清可以保护小鼠免受皮肤坏死和侵袭性感染，但对皮肤脓肿没有明显的作用，这表明单独的抗体可能不足以在该模型中提供保护。因此，用SA裂解物制备的免疫可产生有效的抗体和T细胞反应，并在全身和皮肤葡萄球菌感染模型中提供保护。
Staphylococcus aureusis a very important human pathogen that causes significant morbidity and mortality worldwide. Several vaccine clinical trials based on generating antibody against staphylococcal surface polysaccharides or proteins have been unsuccessful. A killed whole cell lysate preparation (SaWCA) was made by lysing a USA 300 strain with lysostaphin followed by sonication and harvest of the supernatant fraction. Immunization with SaWCA and cholera toxin (CT) generated robust IL-17A but relatively modest antibody responses, and provided protection in the skin abscess but not in the dermonecrosis or invasive infection model. In contrast, parenteral immunization with SaWCA and alum produced robust antibody and IL-17A responses and protected mice in all three models. Sera generated after immunization with SaWCA had measurable antibodies directed against six tested conserved surface proteins, and promoted opsonophagocytosis activity (OPA) against twoS. aureusstrains. Passive transfer of SaWCA-immune serum protected mice against dermonecrosis and invasive infection but provided no demonstrable effect against skin abscesses, suggesting that antibodies alone may not be sufficient for protection in this model. Thus, immunization with a SA lysate preparation generates potent antibody and T cell responses, and confers protection in systemic and cutaneous staphylococcal infection models.