The antifungal vaccine derived from the recombinant n terminus of Als3p protects mice against the bacterium Staphylococcus aureus
The antifungal vaccine derived from the recombinant n terminus of Als3p protects mice against the bacterium Staphylococcus aureus
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DOI：
10.1128/iai.00700-08
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发表时间：
2008-10-01
影响因子：
3.1
通讯作者：
Edwards, John E., Jr.
中科院分区：
文献类型：
--
作者：
Spellberg, Brad;Ibrahim, Ashraf S.;Edwards, John E., Jr.
用念珠菌粘附素Als 3 p（rAls 3 p-N）的重组N末端疫苗接种保护小鼠免于致死性念珠菌血症。Als 3 p在结构上也类似于识别来自金黄色葡萄球菌的粘附基质分子粘附素、凝集因子的微生物表面组分。为了确定跨王国疫苗接种的可能性，我们用rAls 3 p-N或阴性对照蛋白免疫小鼠，并通过尾静脉用S.金黄色葡萄球菌或其它革兰氏阳性或革兰氏阴性病原体。rAls 3 p-N疫苗，但既不是破伤风类毒素也不是相关的Als蛋白（Als 5 p），提高了随后感染多种临床分离的S.金黄色葡萄球菌，包括耐甲氧西林菌株。rAls 3 p-N疫苗对S.当与氢氧化铝佐剂组合时，然而，该疫苗并没有提高感染其他细菌病原体的小鼠的存活率。接种疫苗的感染小鼠产生了适度的1型免疫应答。T淋巴细胞缺陷小鼠对S.金黄色葡萄球菌感染，但B淋巴细胞缺陷小鼠没有。此外，在过继转移研究中，来自接种疫苗小鼠的T淋巴细胞而非B淋巴细胞介导了保护作用。被动输注免疫血清无保护作用。这些数据为抗沙门氏菌的跨王国疫苗开发提供了基础。金黄色葡萄球菌和念珠菌属，它们共同引起200，000例血流感染，仅在美国每年就导致>= 40，000至50，000例死亡。
Vaccination with the recombinant N terminus of the candidal adhesin Als3p (rAls3p-N) protects mice from lethal candidemia. Candidal Als3p also is structurally similar to the microbial surface components recognizing adhesive matrix molecule adhesin, clumping factor, from Staphylococcus aureus. To determine the potential for cross-kingdom vaccination, we immunized mice with rAls3p-N or negative control proteins and challenged them via the tail vein with S. aureus or other gram-positive or gram-negative pathogens. The rAls3p-N vaccine, but neither tetanus toxoid nor a related Als protein (Als5p), improved the survival of vaccinated mice subsequently infected with multiple clinical isolates of S. aureus, including methicillin-resistant strains. The rAls3p-N vaccine was effective against S. aureus when combined with aluminum hydroxide adjuvant. However, the vaccine did not improve the survival of mice infected with other bacterial pathogens. Vaccinated, infected mice mounted moderated type 1 immune responses. T lymphocyte-deficient mice were more susceptible to S. aureus infection, but B lymphocyte-deficient mice were not. Furthermore, T but not B lymphocytes from vaccinated mice mediated protection in adoptive transfer studies. The passive transfer of immune serum was not protective. These data provide the foundation for cross-kingdom vaccine development against S. aureus and Candida, which collectively cause 200,000 bloodstream infections resulting in >= 40,000 to 50,000 deaths annually in the United States alone.