Yeaman Michael R, Filler Scott G, Schmidt Clint S, Ibrahim Ashraf S, Edwards John E, Hennessey John P
Department of Medicine, David Geffen School of Medicine at UCLA , Los Angeles, CA , USA ; Division of Infectious Diseases, Harbor-UCLA Medical Center , Torrance, CA , USA ; Division of Molecular Medicine, Harbor-UCLA Medical Center , Torrance, CA , USA ; St. John's Cardiovascular Research Center, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center , Torrance, CA , USA.
Department of Medicine, David Geffen School of Medicine at UCLA , Los Angeles, CA , USA ; Division of Infectious Diseases, Harbor-UCLA Medical Center , Torrance, CA , USA ; St. John's Cardiovascular Research Center, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center , Torrance, CA , USA.
Front Immunol. 2014 Sep 26;5:463. doi: 10.3389/fimmu.2014.00463. eCollection 2014.
Recent perspectives forecast a new paradigm for future "third generation" vaccines based on commonalities found in diverse pathogens or convergent immune defenses to such pathogens. For Staphylococcus aureus, recurring infections and a limited success of vaccines containing S. aureus antigens imply that native antigens induce immune responses insufficient for optimal efficacy. These perspectives exemplify the need to apply novel vaccine strategies to high-priority pathogens. One such approach can be termed convergent immunity, where antigens from non-target organisms that contain epitope homologs found in the target organism are applied in vaccines. This approach aims to evoke atypical immune defenses via synergistic processes that (1) afford protective efficacy; (2) target an epitope from one organism that contributes to protective immunity against another; (3) cross-protect against multiple pathogens occupying a common anatomic or immunological niche; and/or (4) overcome immune subversion or avoidance strategies of target pathogens. Thus, convergent immunity has a potential to promote protective efficacy not usually elicited by native antigens from a target pathogen. Variations of this concept have been mainstays in the history of viral and bacterial vaccine development. A more far-reaching example is the pre-clinical evidence that specific fungal antigens can induce cross-kingdom protection against bacterial pathogens. This trans-kingdom protection has been demonstrated in pre-clinical studies of the recombinant Candida albicans agglutinin-like sequence 3 protein (rAls3) where it was shown that a vaccine containing rAls3 provides homologous protection against C. albicans, heterologous protection against several other Candida species, and convergent protection against several strains of S. aureus. Convergent immunity reflects an intriguing new approach to designing and developing vaccine antigens and is considered here in the context of vaccines to target S. aureus.
近期观点基于不同病原体中发现的共性或针对此类病原体的趋同免疫防御，预测了未来“第三代”疫苗的新模式。对于金黄色葡萄球菌，反复感染以及含金黄色葡萄球菌抗原的疫苗成效有限，这意味着天然抗原诱导的免疫反应不足以实现最佳疗效。这些观点例证了将新型疫苗策略应用于高优先级病原体的必要性。一种这样的方法可称为趋同免疫，即把来自非靶标生物体、含有在靶标生物体中发现的表位同源物的抗原应用于疫苗。这种方法旨在通过协同过程引发非典型免疫防御，这些过程能够：（1）提供保护效力；（2）靶向一种生物体的表位，该表位有助于对另一种生物体产生保护性免疫；（3）对占据共同解剖学或免疫学生态位的多种病原体进行交叉保护；和/或（4）克服靶标病原体的免疫颠覆或逃避策略。因此，趋同免疫有潜力促进通常由靶标病原体的天然抗原无法引发的保护效力。这一概念的变体一直是病毒和细菌疫苗开发历史中的主流。一个更具深远意义的例子是临床前证据表明特定真菌抗原可诱导针对细菌病原体的跨界保护。这种跨界保护已在重组白色念珠菌凝集素样序列3蛋白（rAls3）的临床前研究中得到证实，研究表明含rAls3的疫苗可提供针对白色念珠菌的同源保护、针对其他几种念珠菌属的异源保护以及针对多种金黄色葡萄球菌菌株的趋同保护。趋同免疫反映了一种设计和开发疫苗抗原的有趣新方法，本文将在针对金黄色葡萄球菌的疫苗背景下对此进行探讨。
