Fusco William G, Choudhary Neelima R, Routh Patty A, Ventevogel Melissa S, Smith Valerie A, Koch Gary G, Almond Glen W, Orndorff Paul E, Sempowski Gregory D, Leduc Isabelle
Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA.
Vaccine. 2014 Jun 24;32(30):3752-8. doi: 10.1016/j.vaccine.2014.05.031. Epub 2014 May 18.
Adherence of pathogens to cellular targets is required to initiate most infections. Defining strategies that interfere with adhesion is therefore important for the development of preventative measures against infectious diseases. As an adhesin to host extracellular matrix proteins and human keratinocytes, the trimeric autotransporter adhesin DsrA, a proven virulence factor of the Gram-negative bacterium Haemophilus ducreyi, is a potential target for vaccine development. A recombinant form of the N-terminal passenger domain of DsrA from H. ducreyi class I strain 35000HP, termed rNT-DsrAI, was tested as a vaccine immunogen in the experimental swine model of H. ducreyi infection. Viable homologous H. ducreyi was not recovered from any animal receiving four doses of rNT-DsrAI administered with Freund's adjuvant at two-week intervals. Control pigs receiving adjuvant only were all infected. All animals receiving the rNT-DsrAI vaccine developed antibody endpoint titers between 3.5 and 5 logs. All rNT-DsrAI antisera bound the surface of the two H. ducreyi strains used to challenge immunized pigs. Purified anti-rNT-DsrAI IgG partially blocked binding of fibrinogen at the surface of viable H. ducreyi. Overall, immunization with the passenger domain of the trimeric autotransporter adhesin DsrA accelerated clearance of H. ducreyi in experimental lesions, possibly by interfering with fibrinogen binding.
大多数感染的发生都需要病原体粘附到细胞靶点上。因此,确定干扰粘附的策略对于开发传染病预防措施至关重要。作为一种与宿主细胞外基质蛋白和人角质形成细胞的粘附素,三聚体自转运粘附素DsrA是革兰氏阴性菌杜克雷嗜血杆菌已证实的毒力因子,是疫苗开发的潜在靶点。来自杜克雷嗜血杆菌I类菌株35000HP的DsrA N端乘客结构域的重组形式,称为rNT-DsrAI,在杜克雷嗜血杆菌感染的实验猪模型中作为疫苗免疫原进行了测试。在任何接受四剂rNT-DsrAI并每隔两周与弗氏佐剂一起给药的动物中,均未检测到活的同源杜克雷嗜血杆菌。仅接受佐剂的对照猪均被感染。所有接受rNT-DsrAI疫苗的动物产生的抗体终点效价在3.5至5个对数之间。所有rNT-DsrAI抗血清均与用于攻击免疫猪的两种杜克雷嗜血杆菌菌株的表面结合。纯化的抗rNT-DsrAI IgG部分阻断了纤维蛋白原在活的杜克雷嗜血杆菌表面的结合。总体而言,用三聚体自转运粘附素DsrA的乘客结构域进行免疫接种可能通过干扰纤维蛋白原结合,加速了实验性病变中杜克雷嗜血杆菌的清除。