Pier Gerald B
Division of Infectious Diseases; Department of Medicine; Brigham and Women's Hospital; Harvard Medical School; Boston, MA USA.
Hum Vaccin Immunother. 2013 Sep;9(9):1865-76. doi: 10.4161/hv.25182. Epub 2013 Jun 21.
Developing a universal vaccine for S. aureus is a top priority but to date we have only had failures in human clinical trials. Given the plethora of bacterial virulence factors, broad range of the health of humans at-risk for infections, lack of any information regarding immune effectors mediating protection for any manifestation of S. aureus infection and overall competence of this organism as a colonizer, commensal and pathogen, we may just simply have to accept the fact that we will not get a universal vaccine. Antigenic variation is a major challenge for some vaccine targets and for many conserved targets the organism can easily decrease or even eliminate expression to avoid immune effectors without compromise to infectivity and ability to cause disease. Studies of human immune responses similarly have been unable to identify any clear mediators of immunity and data from such studies can only eliminate those found not to be associated with protection or that might serve as a marker for individuals with a higher level of resistance to infection. Animal studies are not predictive of success in humans and unlikely will be except in hindsight if and when we develop an efficacious vaccine. Successful vaccines for other bacteria based on capsular polysaccharides have not worked to date for S. aureus, and laboratory studies combining antibody to the major capsular serotypes and the other S. aureus surface polysaccharide, poly-N-acetyl glucosamine, unexpectedly showed interference not augmentation of immunity. Potential pathways toward vaccine development do exist but for the foreseeable future will be based on empiric approaches derived from laboratory-based in vitro and animal tests and not on inducing a known immune effector that predicts human resistance to infection.
开发一种针对金黄色葡萄球菌的通用疫苗是当务之急，但迄今为止，我们在人体临床试验中均告失败。鉴于细菌毒力因子众多，易感染人群健康状况差异大，缺乏关于介导金黄色葡萄球菌感染任何表现形式保护作用的免疫效应器的信息，以及该生物体作为定植菌、共生菌和病原体的整体特性，我们可能不得不接受这样一个事实，即我们无法研制出通用疫苗。抗原变异对某些疫苗靶点来说是一项重大挑战，对于许多保守靶点，该生物体能够轻松降低甚至消除其表达，以避开免疫效应器，同时又不影响其感染性和致病能力。对人类免疫反应的研究同样未能确定任何明确的免疫介质，此类研究数据只能排除那些被发现与保护无关或可能作为对感染具有较高抵抗力个体标志物的因素。动物研究无法预测在人体中的成功情况，而且除了在我们研制出有效疫苗之后的事后诸葛亮式回顾外，不太可能做到这一点。基于荚膜多糖的针对其他细菌的成功疫苗迄今对金黄色葡萄球菌不起作用，而且将针对主要荚膜血清型的抗体与金黄色葡萄球菌的另一种表面多糖聚 - N - 乙酰葡糖胺相结合的实验室研究意外地显示，这会干扰而非增强免疫力。疫苗开发的潜在途径确实存在，但在可预见的未来将基于源自实验室体外和动物试验的经验性方法，而不是基于诱导一种已知的预测人类对感染抵抗力的免疫效应器。
