2016 年 12 月,复旦大学附属眼耳鼻喉科医院陈泽宇等在 Frontiers of Medicine 发表《 Hib 多糖与 PsaA 蛋白结合疫苗的免疫原性及其在小鼠体内预防由肺炎球菌导致的中耳炎的免疫保护作用》。 Frontiers of Medicine, 2016, 10(4): 490-498 doi: 10.1007/s11684-016-0470-y 摘要 本研究的目的是研制 b 型流感嗜血杆菌( Hib )多糖与肺炎球菌表面黏附素( PsaA )结合疫苗,并评价其在幼龄小鼠体内的免疫原性和免疫保护作用。通过基因工程技术制备重组 PsaA 蛋白后将之与 Hib 多糖偶联结合制备得到 Hib-PsaA 结合疫苗。将 45 只 3 ~ 5 周龄的 BALB/c 小鼠随机分成 3 组,每组 15 只,其中两组分别接种 Hib-PsaA 结合疫苗、 Hib-TT 结合疫苗(市售商品疫苗),另有一组接种 PBS (磷酸盐缓冲液)作为对照。 Hib-PsaA 组与 PBS 组接种完成后以肺炎球菌攻击中耳。结果显示,接种 Hib-PsaA 疫苗的小鼠体内产生了较高效价的抗 PsaA 抗体 IgG 和抗 Hib 多糖抗体 IgG ,其产生的抗 Hib 多糖抗体滴度与 Hib-TT 组的抗 Hib 多糖抗体滴度相似。肺炎球菌攻击小鼠中耳后两组小鼠细菌清除率的结果及中耳炎症反应的程度的差异表明 Hib-PsaA 结合疫苗对肺炎球菌导致的小鼠急性中耳炎起到了有效的预防作用。本项研究表明,溴化氰活化法可成功地将 Hib 多糖与 PsaA 蛋白偶联结合,制备的新型 Hib-PsaA 结合疫苗在幼龄小鼠体内能诱导产生明显的针对 Hib 多糖和 PsaA 的免疫反应,并能有效地预防肺炎球菌导致的急性中耳炎。 关键词 结合疫苗;肺炎球菌表面黏附素 A ; b 型流感嗜血杆菌;免疫原性;中耳炎 Abstract This study evaluated the immunogenicity andprotective immunity of a Hemophilus influenzae b (Hib) polysaccharide conjugatevaccine with the pneumococcal surface adhesin A (PsaA) protein carrier in youngmice. The Hib polysaccharide was conjugated with the rPsaA protein carrier,which was produced using recombinant DNA technology. A total of 15 young miceaged 3 weeks to 5 weeks were immunized with the conjugate vaccine, and another15 young mice of the same age were immunized with the licensed Hib-tetanus toxoid(TT) vaccine. Furthermore, the third group of 15 young mice was inoculated withphosphate buffer saline as control. The immunized mice were inoculated withpneumococcus in the middle ear. Results showed that IgG antibody responsesagainst both the PsaA protein and Hib polysaccharide were observed in theHib-PsaA group. However, no statistical difference was observed in the titer ofIgG against the Hib polysaccharide between Hib-PsaA and Hib-TT groups. Theelimination rate of pneumococcus and the inflammation of the middle ear showedthe effectiveness of protective immunity against otitis media caused bypneumococcus. Our results suggest that the Hib polysaccharide can besuccessfully conjugated with rPsaA via amide condensation. This new Hib-PsaA conjugatevaccine can induce both anti-PsaA and anti-Hib immune responses in young miceand elicit effective protection against acute otitis media caused bypneumococcus. Keywords conjugate vaccine; pneumococcal surface adhesin A; Hemophilus influenzae b; immunogenicity; otitis media Corresponding Authors Zeyu Chen Cite this article Zeyu Chen,RongGuo,Jianghong Xu, et al. Immunogenicity and protective immunity against otitismedia caused by pneumococcus in mice of Hib conjugate vaccine with PsaA proteincarrier . Front. Med., 2016, 10(4): 490-498. 更多信息,详见 http://journal.hep.com.cn/fmd/EN/10.1007/s11684-016-0470-y 感谢关注本刊博文,欢迎转载或引用。