影响革兰氏阳性共生载体表达的重组蛋白表面表达和免疫原性的因素分析。
Analysis of factors affecting surface expression and immunogenicity of recombinant proteins expressed by gram-positive commensal vectors.
作者信息
Bolken Tové C, Franke Christine A, Jones Kevin F, Bell Richard H, Swanson Ryan M, King David S, Fischetti Vincent A, Hruby Dennis E
机构信息
SIGA Technologies Inc., Corvallis, Oregon 97333, USA.
出版信息
Infect Immun. 2002 May;70(5):2487-91. doi: 10.1128/IAI.70.5.2487-2491.2002.
Abstract
Several key protein structural attributes were altered in an effort to optimize expression and immunogenicity of a foreign protein (M protein from Streptococcus pyogenes) exposed on the surface of Streptococcus gordonii commensal bacterial vectors: (i) a shorter N-terminal region, (ii) the addition of a 94-amino-acid spacer, and (iii) the addition of extra C-repeat regions (CRR) from the M6 protein. A decrease in the amount of cell surface M6 was observed upon deletion of 10 or more amino acid residues at the N terminus. On the other hand, reactivity of monoclonal antibody to surface M6 increased with the addition of the spacer adjacent to the proline- and glycine-rich region, and an increase in epitope dosage was obtained by adding another CRR immediately downstream of the original CRR. The results obtained should facilitate the design of improved vaccine candidates using this antigen delivery technology.
摘要
为优化暴露在共生戈登链球菌载体表面的外源蛋白（化脓性链球菌的M蛋白）的表达和免疫原性，对几个关键的蛋白质结构属性进行了改变：（i）较短的N端区域；（ii）添加一个94个氨基酸的间隔区；（iii）添加来自M6蛋白的额外C重复区域（CRR）。在N端缺失10个或更多氨基酸残基后，观察到细胞表面M6的量减少。另一方面，单克隆抗体对表面M6的反应性随着在富含脯氨酸和甘氨酸区域附近添加间隔区而增加，并且通过在原始CRR的紧邻下游添加另一个CRR获得了表位剂量的增加。所获得的结果应有助于使用这种抗原递送技术设计改进的候选疫苗。
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