Department of Pediatrics, Columbia University, New York, NY, United States.
Department of Medicine, David Geffen School of Medicine at University of California Loss Angeles (UCLA), Los Angeles, CA, United States.
Front Cell Infect Microbiol. 2022 Dec 27;12:1060810. doi: 10.3389/fcimb.2022.1060810. eCollection 2022.
Despite meritorious attempts, a vaccine that prevents infection or mitigates severity has not yet achieved efficacy endpoints in prospective, randomized clinical trials. This experience underscores the complexity of host- interactions, which appear to be greater than many other bacterial pathogens against which successful vaccines have been developed. It is increasingly evident that employs strategic countermeasures to evade or exploit human immune responses. From entering host cells to persist in stealthy intracellular reservoirs, to sensing the environmental milieu and leveraging bacterial or host metabolic products to reprogram host immune responses, poses considerable challenges for the development of effective vaccines. The fact that this pathogen causes distinct types of infections and can undergo transient genetic, transcriptional or metabolic adaptations that do not occur compounds challenges in vaccine development. Notably, the metabolic versatility of both bacterial and host immune cells as they compete for available substrates within specific tissues inevitably impacts the variable repertoire of gene products that may or may not be vaccine antigens. In this respect, has chameleon phenotypes that have alluded vaccine strategies thus far. Nonetheless, a number of recent studies have also revealed important new insights into pathogenesis vulnerabilities of . A more detailed understanding of host protective immune defenses versus adaptive immune evasion mechanisms may offer breakthroughs in the development of effective vaccines, but at present this goal remains a very high bar. Coupled with the recent advances in human genetics and epigenetics, newer vaccine technologies may enable such a goal. If so, future vaccines that protect against or mitigate the severity of infections are likely to emerge at the intersection of precision and personalized medicine. For now, the development of vaccines or alternative therapies that reduce mortality and morbidity must continue to be pursued.
尽管进行了有益的尝试，但在前瞻性、随机临床试验中，还没有一种疫苗能达到预防感染或减轻严重程度的疗效终点。这一经验突显了宿主相互作用的复杂性，这种复杂性似乎比许多其他已成功开发疫苗的细菌病原体更大。越来越明显的是， 利用策略性的对策来逃避或利用人体免疫反应。从进入宿主细胞到潜伏在隐蔽的细胞内储库，再到感知环境并利用细菌或宿主代谢产物来重新编程宿主免疫反应， 给有效疫苗的开发带来了相当大的挑战。事实上，这种病原体引起不同类型的感染，并且可以经历短暂的遗传、转录或代谢适应，而这些适应在 中不会发生，这增加了疫苗开发的挑战。值得注意的是，细菌和宿主免疫细胞在特定组织中争夺可用底物时的代谢多功能性，不可避免地会影响可能成为或可能不是疫苗抗原的基因产物的可变 repertoire。在这方面， 具有迄今为止逃避疫苗策略的变色龙表型。尽管如此，最近的一些研究也揭示了 发病机制脆弱性的重要新见解。对宿主保护性免疫防御与 适应性免疫逃避机制的更详细了解可能为开发有效疫苗提供突破，但目前这一目标仍然很高。加上人类遗传学和表观遗传学的最新进展，更新的疫苗技术可能使这一目标成为可能。如果是这样，那么未来预防或减轻 感染严重程度的疫苗很可能会出现在精准和个性化医学的交叉点上。目前，开发 疫苗或降低死亡率和发病率的替代疗法必须继续进行。
