Norovirus derived immunogenic compositions and methods

Abstract

The invention relates to chimeric norovirus VP1 proteins containing the S-domain of VP1 of a first norovirus strain and a P-domain that contains at least a portion of the P-domain of VP1 of a second norovirus strain. The invention also relates to nucleic acids that encode the chimeric VP1 proteins, virus-like particles that contain a chimeric norovirus VP1 protein, and to immunogenic compositions.

1 . A chimeric norovirus viral protein 1 (VP1) comprising the S-domain of the VP1 from a first norovirus strain and at least a portion of the P-domain of the VP1 from a second norovirus strain. 
     
     
         2 . The chimeric norovirus VP1 of  claim 1 , further comprising a linker peptide that operably links the S-domain and the P-domain. 
     
     
         3 . The chimeric norovirus VP1 of  claim 2 , wherein the linker peptide is a linker peptide of the VP1 from the first norovirus strain, from the second norovirus strain, or from a third norovirus strain. 
     
     
         4 . The chimeric norovirus VP1 of  claim 1 , which has the formula:
   A-S-L-P-B   wherein   A and B are independently absent or any desired amino acid sequence;   S is the S-domain of VP1 from a first norovirus strain;   L is absent or a linker peptide;   P is a norovirus VP1 P-domain; wherein at least a portion of the P-domain is from a second norovirus strain.   
     
     
         5 . The chimeric VP1 of  claim 4 , wherein L is the linker peptide of VP1 from the first norovirus strain, from the second norovirus strain or from a third norovirus strain. 
     
     
         6 . The chimeric VP1 of  claim 4 , wherein P is the entire P-domain from a second norovirus strain. 
     
     
         7 . The chimeric VP1 of  claim 4 , wherein P comprises a P1-subdomain, or portion thereof, from the first norovirus strain and a P2-subdomain from a second norovirus strain. 
     
     
         8 . The chimeric VP1 protein of  claim 1 , wherein the first norovirus strain is selected from the group consisting of the norovirus strains listed in Table 1. 
     
     
         9 . The chimeric VP1 protein of  claim 1 , wherein the first norovirus strain is the Snow Mountain strain. 
     
     
         10 . The chimeric VP1 protein of  claim 1 , wherein the second norovirus strain is selected from the group consisting of the norovirus strains listed in Table 1. 
     
     
         11 . The chimeric VP1 protein of  claim 9 , wherein the second norovirus strain is a strain selected from the group consisting of genogroup GII, a norovirus strain from genogroup GI and a norovirus strain from genogroup GIV. 
     
     
         12 . The chimeric VP1 protein of  claim 9 , wherein the second norovirus strain is selected from the group consisting of a norovirus strain from genogroup GII, and a norovirus strain from genogroup GI. 
     
     
         13 . The chimeric VP1 protein of  claim 12 , wherein the second norovirus strain is Norwalk virus, GII.4.2006a, or New Orleans. 
     
     
         14 . A norovirus virus like particle (VLP) comprising a chimeric VP1 protein of  claim 1 . 
     
     
         15 . A monovalent norovirus virus like particle (VLP) comprising a chimeric VP1 protein of  claim 1 . 
     
     
         16 . A multivalent norovirus virus like particle (VLP) comprising a chimeric VP1 protein is of  claim 1 . 
     
     
         17 . The multivalent VLP according to  claim 16 , wherein the VLP comprises two or more different chimeric VP1 proteins. 
     
     
         18 . An immunogenic composition comprising a chimeric VP1 protein of  claim 1 . 
     
     
         19 . An immunogenic composition comprising a VLP of  claim 14 . 
     
     
         20 . An immunogenic composition comprising a monovalent VLP of  claim 15 . 
     
     
         21 . An immunogenic composition comprising a multivalent VLP of  claim 16 . 
     
     
         22 . An immunogenic composition, comprising two or more different monovalent VLPs of  claim 15 . 
     
     
         23 . A recombinant nucleic acid encoding a chimeric VP1 protein of  claim 1 . 
     
     
         24 . The recombinant nucleic acid of  claim 23 , wherein the recombinant nucleic acid comprises a vector. 
     
     
         25 . The recombinant nucleic acid of  claim 23 , wherein the recombinant nucleic acid is self-replicating. 
     
     
         26 . An immunogenic composition comprising a recombinant nucleic acid of  claim 23 . 
     
     
         27 . A recombinant host cell comprising a recombinant nucleic acid of  claim 23 . 
     
     
         28 . The recombinant host cell of  claim 27 , wherein the host cell is selected from the group consisting of insect cells, mammalian cells, avian cells, bacteria, yeast cells, Tetrahymena cells and combinations thereof. 
     
     
         29 . A method of producing a chimeric norovirus VP1 protein and/or VLP, comprising culturing a recombinant host cell of  claim 28  under conditions whereby the recombinant nucleic acid is expressed and chimeric VP1 protein is produced. 
     
     
         30 . The method of  claim 29 , wherein the recombinant host cell is maintained under conditions suitable for formation of VLPs. 
     
     
         31 . The method of  claim 29 , further comprising isolating the chimeric norovirus VP1 protein and/or VLPs from the culture media and/or the recombinant host cells. 
     
     
         32 . The method of  claim 31 , wherein VLPs are isolated. 
     
     
         33 . The method of  claim 32 , wherein the VLPs are isolated using a sucrose cushion or sucrose gradient. 
     
     
         34 . The chimeric VP1 of  claim 5 , wherein P is the entire P-domain from a second norovirus strain. 
     
     
         35 . The chimeric VP1 of  claim 5 , wherein P is the entire P-domain from a second norovirus strain. 
     
     
         36 . A norovirus virus like particle (VLP) comprising a chimeric VP1 protein of  claim 2 . 
     
     
         37 . A monovalent norovirus virus like particle (VLP) comprising a chimeric VP1 protein is of  claim 2 . 
     
     
         38 . A multivalent norovirus virus like particle (VLP) comprising a chimeric VP1 protein is of  claim 2 . 
     
     
         39 . The multivalent VLP of  claim 38 , wherein the VLP comprises two or more different chimeric VP1 proteins. 
     
     
         40 . An immunogenic composition comprising a chimeric VP1 protein of  claim 2 . 
     
     
         41 . An immunogenic composition comprising a VLP of  claim 36 . 
     
     
         42 . An immunogenic composition comprising a monovalent VLP of  claim 37 . 
     
     
         43 . An immunogenic composition comprising a multivalent VLP of  claim 38 . 
     
     
         44 . An immunogenic composition, comprising two or more different monovalent VLPs of  claim 37 . 
     
     
         45 . A recombinant nucleic acid encoding a chimeric VP1 protein of  claim 2 .