Department of Medicine, Division of Dermatology, University of California, San Diego, San Diego, CA 92121, USA.
Vaccine. 2011 Apr 12;29(17):3230-8. doi: 10.1016/j.vaccine.2011.02.036. Epub 2011 Feb 26.
Propionibacterium acnes (P. acnes) bacteria play a key role in the pathogenesis of acne vulgaris. Although our previous studies have demonstrated that vaccines targeting a surface sialidase or bacterial particles exhibit a preventive effect against P. acnes, the lack of therapeutic activities and incapability of neutralizing secretory virulence factors motivate us to generate novel immunotherapeutics. In this study, we develop an immunotherapeutic antibody to secretory Christie-Atkins-Munch-Peterson (CAMP) factor of P. acnes. Via agroinfiltration, P. acnes CAMP factor was encapsulated into the leaves of radishes. ICR mice intranasally immunized with whole leaves expressing CAMP factor successfully produced neutralizing antibodies that efficiently attenuated P. acnes-induced ear swelling and production of macrophage-inflammatory protein-2. Passive neutralization of CAMP factor enhanced immunity to eradicate P. acnes at the infection site without influencing bacterial growth elsewhere. We propose that CAMP factor is a novel therapeutic target for the treatment of various P. acnes-associated diseases and highlight the concept of neutralizing P. acnes virulence without disturbing the bacterial commensalism in human microbiome.
痤疮丙酸杆菌(P. acnes)细菌在寻常痤疮的发病机制中起关键作用。尽管我们之前的研究表明,针对表面唾液酸酶或细菌颗粒的疫苗具有预防 P. acnes 的作用,但缺乏治疗活性和中和分泌性毒力因子的能力促使我们开发新型免疫疗法。在这项研究中,我们开发了一种针对痤疮丙酸杆菌分泌性克里斯蒂-阿特金斯-芒奇-彼得森(CAMP)因子的免疫治疗抗体。通过农杆菌浸润,将 P. acnes CAMP 因子包封在萝卜叶片中。用表达 CAMP 因子的全叶片经鼻腔免疫的 ICR 小鼠成功产生了中和抗体,有效减轻了 P. acnes 诱导的耳部肿胀和巨噬细胞炎症蛋白-2 的产生。CAMP 因子的被动中和增强了免疫力,可在不影响其他部位细菌生长的情况下消除感染部位的 P. acnes。我们提出 CAMP 因子是治疗各种与 P. acnes 相关疾病的新型治疗靶标,并强调了中和 P. acnes 毒力而不干扰人类微生物组中细菌共生的概念。