Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Department of Immunology of Infectious Diseases, Laboratory of Medical Microbiology, Wroclaw, Poland.
Department of Medical Microbiology, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland.
Sci Rep. 2018 Sep 17;8(1):13946. doi: 10.1038/s41598-018-32193-9.
Clostridium difficile (CD) infections are a growing threat due to the strain resistance to antibiotic treatment and the emergence of hypervirulent strains. One solution to this problem is the search for new vaccine antigens, preferably surface-localized that will be recognized by antibodies at an early stage of colonization. The purpose of the study was to assess the usefulness of novel immunoreactive surface proteins (epitopes) as potential vaccine antigens. Such approach might be tough to pursue since pathogens have acquired strategies to subvert adaptive immune response to produce humoral response against non-essential proteins for their survival. In this study CD surface proteins were isolated, immunoreactive proteins identified and mapped to select potential epitopes. The results of the study exclude the use of CD glyceraldehyde 3-phosphate dehydrogenase as a vaccine antigen, especially as a whole protein. Sequences P9 (AAGNIVPNTTGAAKAI) and P10 (KGKLDGAAQRVPVVTG) recognized by patients sera are conserved and widespread among CD strains. They show cross-reactivity with sera of people suffering from other bacterial infections and are recognized by sera of autoimmune disease patients. Our study documents that special care in analyzing the sequence of new epitope should be taken to avoid side effects prior to consider it as a vaccine antigen.
艰难梭菌(CD)感染是一个日益严重的威胁,因为菌株对抗生素治疗的耐药性以及高毒力菌株的出现。解决这个问题的一个方法是寻找新的疫苗抗原,最好是表面定位的,以便在定植的早期被抗体识别。本研究的目的是评估新型免疫反应性表面蛋白(表位)作为潜在疫苗抗原的有用性。由于病原体已经采取了策略来颠覆适应性免疫反应,以产生针对其生存非必需蛋白的体液反应,因此这种方法可能很难实施。在这项研究中,分离了 CD 表面蛋白,鉴定了免疫反应性蛋白,并对选择的潜在表位进行了定位。该研究的结果排除了使用 CD 甘油醛 3-磷酸脱氢酶作为疫苗抗原,尤其是整个蛋白作为疫苗抗原的可能性。被患者血清识别的序列 P9(AAGNIVPNTTGAAKAI)和 P10(KGKLDGAAQRVPVVTG)在 CD 菌株中保守且广泛存在。它们与患有其他细菌感染的人的血清发生交叉反应,并被自身免疫性疾病患者的血清识别。我们的研究证明,在分析新表位的序列时,应特别注意避免副作用,然后再考虑将其作为疫苗抗原。