Antigen-Norovirus P-domain monomers and dimers, antigen Norovirus P-particle molecules, and methods for their making and use

摘要

A substituted Norovirus capsid protein monomer, having only the P-domain, includes a foreign antigen inserted into one or more of three surface loops present on each P-domain monomer by molecular cloning. The antigen-P-domain monomer can assemble spontaneously into an octahedral, antigen-Norovirus P-particle, composed of 24 copies of the monomer. Each substituted P-domain monomer can contain one to three copies of the foreign antigen, for a total of 24-72 antigen copies on each antigen-P-particle. The antigen-P-particle is useful in methods for diagnosing, immunizing and treating individuals infected with a foreign virus and as a carrier for development of vaccines against many infectious and non-infectious diseases. The substituted monomer can be readily produced in E. coli and yeast, are highly stable and tolerate a wide range of physio-chemical conditions. The P-particle-VP8 chimeras may also serve as a dual vaccine, for example, against both rotavirus and norovirus.