Helpful dirt: Why diphtheria toxoid vaccines may also protect against non-toxigenic Corynebacterium diphtheriae strains

Diphtheria toxoid vaccines are among the oldest and safest vaccines known. The basic principle of production is the inactivation of purified diphtheria toxin by formaldehyde cross-linking, which converts the potentially fatal toxin in a completely harmless protein aggregate, which is still immunogenic. Since in addition to diphtheria toxin also other proteins might be secreted by Corynebacterium diphtheriae, we assumed that diphtheria toxoid might not be the only component present in the vaccine. Therefore, we established a protocol to reverse formaldehyde cross-linking and carried out mass spectrometric analyses. Different secreted, membrane-associated and cytoplasmic proteins of C. diphtheriae were detected in several vaccine preparations from across the world. Western blot analyses indicated that these are immunogenic and may therefore support protection against C. diphtheriae. Furthermore, we could show that the vaccines also induce antibodies directed against diphtheria toxin secreted by Corynebacterium ulcerans, an emerging pathogen evoking diphtheria-like illness and skin infections.白喉类毒素疫苗（diphtheria toxoid vaccine）是目前已知最古老且最安全的疫苗之一。其生产的基本原理是通过甲醛交联使纯化白喉毒素失活，将具有致命性的毒素转化为完全无害但仍保留免疫原性的蛋白质聚集体。由于除白喉毒素外，白喉棒状杆菌（Corynebacterium diphtheriae）还可能分泌其他蛋白质，因此我们推测白喉类毒素或许并非疫苗中仅有的成分。为此，我们建立了甲醛交联逆转方案，并开展了质谱分析（mass spectrometric analyses）。在全球多地的多批疫苗制剂中，我们均检测到了白喉棒状杆菌的多种分泌型、膜结合型及胞质型蛋白质。蛋白质印迹（Western blot）分析结果显示，这些蛋白质均具有免疫原性，因此可能有助于机体抵御白喉棒状杆菌的感染。此外，我们还证实，该类疫苗还可诱导针对溃疡棒状杆菌（Corynebacterium ulcerans）分泌的白喉毒素的抗体，溃疡棒状杆菌是一种可引发类白喉疾病及皮肤感染的新发病原体。