Spellberg Brad, Ibrahim Ashraf S, Yeaman Michael R, Lin Lin, Fu Yue, Avanesian Valentina, Bayer Arnold S, Filler Scott G, Lipke Peter, Otoo Henry, Edwards John E
Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor, University of California at Los Angeles Medical Center, Torrance, California 90502, USA.
Infect Immun. 2008 Oct;76(10):4574-80. doi: 10.1128/IAI.00700-08. Epub 2008 Jul 21.
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.
用念珠菌粘附素Als3p的重组N端（rAls3p-N）进行疫苗接种可保护小鼠免受致死性念珠菌血症的侵害。念珠菌Als3p在结构上也类似于金黄色葡萄球菌的微生物表面成分识别粘附基质分子粘附素、聚集因子。为了确定跨王国疫苗接种的潜力，我们用rAls3p-N或阴性对照蛋白免疫小鼠，并通过尾静脉用金黄色葡萄球菌或其他革兰氏阳性或革兰氏阴性病原体对它们进行攻击。rAls3p-N疫苗，而不是破伤风类毒素或相关的Als蛋白（Als5p），提高了随后感染多种金黄色葡萄球菌临床分离株（包括耐甲氧西林菌株）的接种小鼠的存活率。rAls3p-N疫苗与氢氧化铝佐剂联合使用时对金黄色葡萄球菌有效。然而，该疫苗并未提高感染其他细菌病原体的小鼠的存活率。接种疫苗并感染的小鼠产生了适度的1型免疫反应。T淋巴细胞缺陷小鼠对金黄色葡萄球菌感染更敏感，但B淋巴细胞缺陷小鼠则不然。此外，在过继转移研究中，接种小鼠的T淋巴细胞而非B淋巴细胞介导了保护作用。免疫血清的被动转移没有保护作用。这些数据为针对金黄色葡萄球菌和念珠菌的跨王国疫苗开发奠定了基础，在美国，这两种病原体每年总共导致200,000例血流感染，造成≥40,000至50,000人死亡。
