MUTATED AND BACTERIOPHAGE T4 NANOPARTICLE ARRAYED F1-V IMMUNOGENS FROM YERSINIA PESTIS AS NEXT GENERATION PLAGUE VACCINES

摘要

Techniques from two basic approaches, structure-based immunogen design and phage T4 nanoparticle delivery, are developed to construct new plague vaccines. The NH2-terminal β-strand of F1 of Yersinia pestis is transplanted to the COOH-terminus of F1 of Yersinia pestis and the NH2-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.

主权项

1. A recombinant protein comprising a mutated F1 antigen of Yersinia pestis, wherein the mutated F1 antigen of Yersinia pestis is developed from a native F1 antigen of Yersinia pestis by the following steps:
deleting an NH2-terminal β-strand of F1 anti en of Yersinia pestis from an NH2-terminus of the native F1 antigen of Yersinia pestis to thereby form an NH2-terminal β-strand deleted F1, fusing the NH2-terminal β-strand of F1 antigen of Yersinia pestis to a COOH-terminus of the NH2-terminal β-strand deleted F1 via a first peptide linker to thereby form an NH2-terminal β-strand transplanted F1, and duplicating an NH2-terminal amino acid sequence of F1 antigen of Yersinia pestis flanking the NH2-terminal β-strand of F1 antigen of Yersinia pestis at a COOH-terminus of the NH2-terminal β-strand transplanted F1 to thereby form a mutated F1 antigen of Yersinia pestis.