NOROVIRUS DERIVED IMMUNOGENIC COMPOSITIONS AND METHODS
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 .