Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
UC San Diego School of Medicine, University of California San Diego, San Diego, CA 92093, USA.
Sci Transl Med. 2023 Oct 4;15(716):eadf9556. doi: 10.1126/scitranslmed.adf9556.
Traditional vaccines are difficult to deploy against the diverse antimicrobial-resistant, nosocomial pathogens that cause health care-associated infections. We developed a protein-free vaccine composed of aluminum hydroxide, monophosphoryl lipid A, and fungal mannan that improved survival and reduced bacterial burden of mice with invasive blood or lung infections caused by methicillin-resistant , vancomycin-resistant , extended-spectrum beta-lactamase-expressing , and carbapenem-resistant strains of , , and The vaccine also conferred protection against the fungi and . Efficacy was apparent by 24 hours and lasted for up to 28 days after a single vaccine dose, with a second dose restoring efficacy. The vaccine acted through stimulation of the innate, rather than the adaptive, immune system, as demonstrated by efficacy in the absence of lymphocytes that were abrogated by macrophage depletion. A role for macrophages was further supported by the finding that vaccination induced macrophage epigenetic alterations that modulated phagocytosis and the inflammatory response to infection. Together, these data show that this protein-free vaccine is a promising strategy to prevent deadly antimicrobial-resistant health care-associated infections.
传统疫苗难以应对导致医源性感染的多种具有抗药性、医院获得性的抗微生物病原体。我们开发了一种由氢氧化铝、单磷酰脂质 A 和真菌甘露聚糖组成的无蛋白疫苗，可提高耐甲氧西林、万古霉素耐药、表达扩展谱β-内酰胺酶和碳青霉烯类耐药的 、 、 引起侵袭性血液或肺部感染的小鼠的存活率并降低其细菌负荷。该疫苗还对真菌 和 提供保护。单次疫苗接种后 24 小时即可显现疗效，并持续长达 28 天，第二次接种可恢复疗效。该疫苗通过刺激先天免疫，而不是适应性免疫系统发挥作用，因为在缺乏淋巴细胞的情况下也具有疗效，而淋巴细胞的缺失可被巨噬细胞耗竭所消除。疫苗诱导巨噬细胞表观遗传改变从而调节吞噬作用和对感染的炎症反应，这进一步支持了巨噬细胞的作用。这些数据表明，这种无蛋白疫苗是预防致命性抗微生物医源性感染的有希望的策略。
