Manipulation of the bluetongue virus tubules for immunogen delivery

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Abstract

A multidisplay vaccine delivery system has been developed that is nonreplicating and has a protein-based particulate structure. The structure is composed of helical tubules comprising multiple copies of a single nonstructural (NS) protein 1 of bluetongue virus. The helical assemblies present the C terminus of the protein on the surface of the tubules, thereby displaying appended residues in regular and repeating arrays. The NS1 protein has been manipulated to carry chosen immunogens at this C terminus, such that many thousands of copies of the foreign immunogen are displayed on the surface of the tubules. The display system can accommodate more than 500 amino acid residues in length without perturbing the basic tubular structure. Many immunogens have been displayed and tested for immunogenicity and have been shown to stimulate both humoral and cellular responses. NS1 tubules represent a safe vaccine-delivery system with great potential in the vaccine arena.

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