公开(公告)号：WO2015004627A1

公开(公告)日：2015-01-15

申请号：PCT/IB2014/063005

申请日：2014-07-10

Applicant: THE CATHOLIC UNIVERSITY OF AMERICA

Inventor： RAO, Venigalla B. ,  TAO, Pan

IPC: C07K14/24 ,  C07K19/00 ,  C12N15/09 ,  A61K39/02

CPC classification number: C07K14/24 ,  A61K39/0291 ,  A61K2039/5256 ,  C07K14/005 ,  C07K2319/21 ,  C07K2319/40 ,  C07K2319/735 ,  C12N2795/10123 ,  Y02A50/407

Abstract: Techniques from two basic approaches, structure-based immunogen design and phage T4 nanoparticle delivery, are developed to construct new plague vaccines. The NH 2 - terminal β-strand of F1 of Yersinia pestis is transplanted to the COOH-terminus of F1 of Yersinia pestis and the NH 2 -- terminus sequence flanking the β-strand of F1 of Yersinia pestis is duplicated to eliminate polymerization but to retain the T cell epitopes. The mutated F1 is fused to the V antigen of Yersinia pestis to thereby form a fusion protein F1mut-V mutant, which produces a completely soluble monomer. The fusion protein F1mut-V is then arrayed on phage T4 nanoparticles via a small outer capsid protein, Soc, from a T4 phage or a T4-related phage. Both the soluble and T4 decorated F1mut-V provided approximately 100% protection to mice and rats against pneumonic plague evoked by high doses of Yersinia pestis CO92.

Abstract translation: 开发了两种基本方法，基于结构的免疫原设计和噬菌体T4纳米颗粒递送的技术来构建新的疫苗疫苗。 将鼠疫耶尔森氏菌的F1的NH2-末端菌株移植到鼠疫耶尔森氏菌的F1的COOH-末端，并且重复鼠疫耶尔森氏菌的F1侧链的NH 2 - 末端序列，以消除聚合反应 保留T细胞表位。 突变的F1融合到鼠疫耶尔森氏菌的V抗原，从而形成融合蛋白F1mut-V突变体，其产生完全可溶的单体。 然后通过T4噬菌体或与T4相关的噬菌体的小外壳衣壳蛋白Soc，将融合蛋白F1mut-V排列在噬菌体T4纳米颗粒上。 可溶性和T4装饰的F1mut-V都能够对小鼠和大鼠提供大约100％的抗高剂量鼠疫耶尔森氏菌CO92诱发的肺炎瘟疫。