Abstract：
Cobalt-porphyrin phospholipid displays recombinant protein antigens on liposome surfaces via antigen polyhistidine-tag (His-tag), and when combined with monophosphorylated lipid A and QS-21 yields the \"CPQ\" vaccine adjuvant system. In this proof of principle study, CPQ was used to generate vaccine prototypes that elicited antibodies for two different alphaviruses (AV). Mice were immunized with computationally designed, His-tagged, physicochemical property consensus (PCPcon) protein antigens representing the variable B-domain of the envelope protein 2 (E2) from the serotype specific Venezuelan Equine Encephalitis Virus (VEEVcon) or a broad-spectrum AV-antigen termed EVCcon. The CPQ adjuvant enhanced the antigenicity of both proteins without eliciting detectable anti-His-tag antibodies. Antibodies elicited from mice immunized with antigens admixed with CPQ showed orders-of-magnitude higher levels of antigen-specific IgG compared to alternative control adjuvants. The ELISA results correlated with antiviral activity against VEEV strain TC83 and more weakly to Chikungunya virus 118/25. Thus, display of E.coli-produced His-tagged E2 protein segments on the surface of immunogenic liposomes elicits high levels of antigen-specific and AV neutralizing antibodies in mice with vaccination, while facilitating vaccine preparation and providing dose-sparing potential.
摘要：
钴卟啉磷脂通过抗原多组氨酸标签（His标签）在脂质体表面展示重组蛋白抗原，当与单磷酸化脂质A和QS-21组合时，会产生“CPQ”疫苗佐剂系统。在这项原理证明研究中，CPQ用于产生疫苗原型,其引发针对两种不同甲病毒(AV)的抗体。用计算设计的小鼠免疫，他的标签，代表血清型特异性委内瑞拉马脑炎病毒（VEEVcon）的包膜蛋白2（E2）的可变B结构域的物理化学性质共有（PCPCcon）蛋白抗原或称为EVCCon的广谱AV抗原。CPQ佐剂增强了两种蛋白质的抗原性，而不会引发可检测的抗His标签抗体。与替代对照佐剂相比,从用与CPQ混合的抗原免疫的小鼠中引发的抗体显示出数量级较高水平的抗原特异性IgG。ELISA结果与针对VEEV毒株TC83的抗病毒活性相关，而与基孔肯雅病毒118/25的抗病毒活性较弱。因此，在免疫原性脂质体表面上展示大肠杆菌产生的His标记的E2蛋白片段，在接种疫苗的小鼠中引发高水平的抗原特异性和AV中和抗体，同时促进疫苗制备和提供剂量节省的潜力。
