Department of Infectious Diseases.
J Infect Dis. 2014 Apr 1;209(7):1116-25. doi: 10.1093/infdis/jit502. Epub 2013 Sep 16.
Pneumococcus, meningococcus, and Haemophilus influenzae cause a similar spectrum of infections in the ear, lung, blood, and brain. They share cross-reactive antigens that bind to the laminin receptor of the blood-brain barrier as a molecular basis for neurotropism, and this step in pathogenesis was addressed in vaccine design.
Biologically active peptides derived from choline-binding protein A (CbpA) of pneumococcus were identified and then genetically fused to L460D pneumolysoid. The fusion construct was tested for vaccine efficacy in mouse models of nasopharyngeal carriage, otitis media, pneumonia, sepsis, and meningitis.
The CbpA peptide-L460D pneumolysoid fusion protein was more broadly immunogenic than pneumolysoid alone, and antibodies were active in vitro against Streptococcus pneumoniae, Neisseria meningitidis, and H. influenzae. Passive and active immunization protected mice from pneumococcal carriage, otitis media, pneumonia, bacteremia, meningitis, and meningococcal sepsis.
The CbpA peptide-L460D pneumolysoid fusion protein was broadly protective against pneumococcal infection, with the potential for additional protection against other meningeal pathogens.
肺炎球菌、脑膜炎奈瑟菌和流感嗜血杆菌在耳部、肺部、血液和脑部引起相似的感染谱。它们具有交叉反应性抗原，这些抗原作为神经嗜性的分子基础与血脑屏障的层粘连蛋白受体结合，这一发病机制步骤在疫苗设计中得到了研究。
从肺炎球菌的胆碱结合蛋白 A（CbpA）中鉴定出具有生物活性的肽，然后将其与 L460D 肺炎球菌溶素融合。在鼻咽携带、中耳炎、肺炎、败血症和脑膜炎的小鼠模型中测试融合构建体的疫苗功效。
CbpA 肽-L460D 肺炎球菌溶素融合蛋白比单独的肺炎球菌溶素更具免疫原性，抗体在体外对肺炎链球菌、脑膜炎奈瑟菌和流感嗜血杆菌具有活性。被动和主动免疫可保护小鼠免受肺炎球菌携带、中耳炎、肺炎、菌血症、脑膜炎和脑膜炎奈瑟菌败血症的侵害。
CbpA 肽-L460D 肺炎球菌溶素融合蛋白对肺炎球菌感染具有广泛的保护作用，并有潜力对其他脑膜病原体提供额外的保护。
