Vaccination Targeting a Surface Sialidase of <em>P. acnes:</em> Implication for New Treatment of Acne Vulgaris

BackgroundAcne vulgaris afflicts more than fifty million people in the United State and the severity of this disorder is associated with the immune response to Propionibacterium acnes (P. acnes). Systemic therapies for acne target P. acnes using antibiotics, or target the follicle with retinoids such as isotretinoin. The latter systemic treatment is highly effective but also carries a risk of side effects including immune imbalance, hyperlipidemia, and teratogenicity. Despite substantial research into potential new therapies for this common disease, vaccines against acne vulgaris are not yet available. Methods and FindingsHere we create an acne vaccine targeting a cell wall-anchored sialidase of P. acnes. The importance of sialidase to disease pathogenesis is shown by treatment of a human sebocyte cell line with recombinant sialidase that increased susceptibility to P. acnes cytotoxicity and adhesion. Mice immunized with sialidase elicit a detectable antibody; the anti-sialidase serum effectively neutralized the cytotoxicity of P. acnes in vitro and P. acnes-induced interleukin-8 (IL-8) production in human sebocytes. Furthermore, the sialidase-immunized mice provided protective immunity against P. acnes in vivo as this treatment blocked an increase in ear thickness and release of pro-inflammatory macrophage inflammatory protein (MIP-2) cytokine. ConclusionsResults indicated that acne vaccines open novel therapeutic avenues for acne vulgaris and other P. acnes-associated diseases.研究背景：寻常痤疮(Acne vulgaris)在美国困扰超过5000万人群，该疾病的严重程度与痤疮丙酸杆菌(Propionibacterium acnes, P. acnes)的免疫应答密切相关。当前痤疮的全身治疗手段多通过抗生素靶向痤疮丙酸杆菌，或使用异维A酸(isotretinoin)等维A酸类药物靶向毛囊。后者虽疗效显著，但存在免疫失衡、高脂血症、致畸性等不良反应风险。尽管针对这一常见疾病的新型治疗方案已有大量研究投入，但针对寻常痤疮的疫苗仍未实现临床应用。 研究方法与结果：本研究开发了一款靶向痤疮丙酸杆菌细胞壁锚定唾液酸酶的痤疮疫苗。通过向人皮脂腺细胞系施加重组唾液酸酶，可提升其对痤疮丙酸杆菌细胞毒性的易感性与黏附能力，由此证实唾液酸酶在疾病发病机制中的关键作用。经唾液酸酶免疫的小鼠可产生可检测到的特异性抗体；抗唾液酸酶血清在体外可有效中和痤疮丙酸杆菌的细胞毒性，并抑制痤疮丙酸杆菌诱导的人皮脂腺细胞白细胞介素-8(interleukin-8, IL-8)分泌。此外，唾液酸酶免疫小鼠可在体内产生针对痤疮丙酸杆菌的保护性免疫：该疗法可阻断小鼠耳厚度增加，并减少促炎性巨噬细胞炎性蛋白(macrophage inflammatory protein, MIP-2)细胞因子的释放。 研究结论：本研究结果表明，痤疮疫苗可为寻常痤疮及其他与痤疮丙酸杆菌相关的疾病开辟全新的治疗途径。