Methods and compositions for norovirus vaccines and diagnostics
AssigneeThe University of North Carolina at Chapel Hill
InventorsLisa Chon Lindesmith, Ralph Steven Baric, Kari Moore Debbink, Eric Francis Donaldson
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Abstract
The present invention is directed to methods and compositions for norovirus therapeutics, such as vaccines, and diagnostics.
Claims33
A chimeric norovirus capsid protein consisting of a norovirus VP1 major capsid protein backbone from norovirus strain GII.4.1974 (SEQ ID NO:1), norovirus strain GII.4.1987 (SEQ ID NO:2), norovirus strain GII.4.1997 (SEQ ID NO:3), norovirus strain GII.4.2002 (SEQ ID NO:4), norovirus strain GII.4.2002a (SEQ ID NO:5), norovirus strain GII.4.2004 (SEQ ID NO:6), norovirus strain GII.4.2005 (SEQ ID NO:7), norovirus strain GII.4.2006 (SEQ ID NO:8), norovirus strain GII.4.2007 (SEQ ID NO:9), norovirus strain GII.4.2008a (SEQ ID NO:10), norovirus strain GII.4.2008s (SEQ ID NO:11), norovirus strain GII.4.2009 (SEQ ID NO:12), or norovirus strain GII.4.2012 (SEQ ID NO:13) in which two or more sets of amino acid residues are substituted into the capsid protein backbone to introduce at least one epitope from each of two or more different norovirus strains of the above norovirus strains, each of which is different from one another and each of which is different from the norovirus strain of the capsid protein backbone,
- wherein at least one of the two or more sets of amino acid residues comprises any one of the following sets of amino acid residues (a)-(f) in any combination:
- a) amino acid residues 391, 393, 394, 395 and 396 (Epitope D);
- b) amino acid residues 234, 310, 316, 484 and 493 (Epitope F);
- and
- c) amino acid residues 327 and 404 (Epitope Fs),
- wherein amino acid residue numbering of (a)-(c) is based on the amino acid sequence of any of SEQ ID NOs:4-13;
- and
- d) amino acid residues 391, 393, 394 and 395 (Epitope D);
- e) amino acid residues 234, 310, 316, 483 and 492 (Epitope F), and
- f) amino acid residues 327 and 403 (Epitope Fs),
- wherein amino acid residue numbering of (d)-(f) is based on the amino acid sequence of SEQ ID NOs:1-3.
A chimeric norovirus capsid protein consisting of a norovirus VP1 major capsid protein backbone from norovirus strain GII.4.1974 (SEQ ID NO:1), norovirus strain GII.4.1987 (SEQ ID NO:2), norovirus strain GII.4.1997 (SEQ ID NO:3), norovirus strain GII.4.2002 (SEQ ID NO:4), norovirus strain GII.4.2002a (SEQ ID NO:5), norovirus strain GII.4.2004 (SEQ ID NO:6), norovirus strain GII.4.2005 (SEQ ID NO:7), norovirus strain GII.4.2006 (SEQ ID NO:8), norovirus strain GII.4.2007 (SEQ ID NO:9), norovirus strain GII.4.2008a (SEQ ID NO:10), norovirus strain GII.4.2008s (SEQ ID NO:11), norovirus strain GII.4.2009 (SEQ ID NO:12), or norovirus strain GII.4.2012 (SEQ ID NO:13),
- in which amino acid residues 234, 310, 316, 484 and 493 (Epitope F) are substituted into the capsid protein backbone, wherein amino acid residue numbering is based on the amino acid sequence of any of SEQ ID NOs:4-13, or
- in which amino acid residues 234, 310, 316, 483 and 492 (Epitope F) are substituted into the capsid protein backbone, wherein amino acid residue numbering is based on the amino acid sequence of any of SEQ ID NOs:1-3, thereby introducing Epitope F from a norovirus strain that is different from the norovirus strain of the capsid protein backbone.
A chimeric norovirus capsid protein consisting of a norovirus VP1 major capsid protein backbone from norovirus strain GII.3 (SEQ ID NO:14), in which one or more, in any combination, of the following sets of amino acid residues (a)-(k) are substituted into the norovirus capsid protein backbone to introduce one or more epitope in any combination, from one or more different norovirus strains, in any combination, as follows:
- a) amino acid residues 294, 296, 297, 298, 368 and 372 (Epitope A) of a norovirus strain having the amino acid sequence of any one of SEQ ID NO:4-13, substituted at positions 294, 310, 311, 312, 381 and 384, respectively, in the amino acid sequence of SEQ ID NO:14;
- b) amino acid residues 333 and 382 (Epitope B) of a norovirus strain having the amino acid sequence of any one of SEQ ID NO:4-13, substituted at positions 347 and 394, respectively, in the amino acid sequence of SEQ ID NO:14;
- c) amino acid residues 340 and 376 (Epitope C) of a norovirus strain having the amino acid sequence of any one of SEQ ID NO:4-13, substituted at positions 353 and 388, respectively, in the amino acid sequence of SEQ ID NO:14;
- d) amino acid residues 391, 393, 394 and 395 (Epitope D) of a norovirus strain having the amino acid sequence of any one of SEQ ID NO:4-13, substituted at positions 403, 404, 405 and 406, respectively, in the amino acid sequence of SEQ ID NO:14;
- e) amino acid residues 407, 412 and 413 (Epitope E) of a norovirus strain having the amino acid sequence of any one of SEQ ID NO:4-13, substituted at positions 415, 420 and 421, respectively, in the amino acid sequence of SEQ ID NO:14;
- f) amino acid residues 234, 310, 316, 484 and 493 (Epitope F) of a norovirus strain having the amino acid sequence of any one of SEQ ID NO:4-13, substituted at positions 234, 324, 330, 492 and 501, respectively, in the amino acid sequence of SEQ ID NO:14;
- and
- g) amino acid residues 327 and 404 (Epitope Fs) of a norovirus strain having the amino acid sequence of any one of SEQ ID NO:4-13, substituted at positions 341 and 412, respectively, in the amino acid sequence of SEQ ID NO:14;
- and
- h) amino acid residues 391, 393, 394 and 395 (Epitope D) of a norovirus strain having the amino acid sequence of any one of SEQ ID NO:1-3, substituted at positions 403, 404, 405 and 406, respectively, in the amino acid sequence of SEQ ID NO:14;
- i) amino acid residues 406, 411 and 412 (Epitope E) of a norovirus strain having the amino acid sequence of any one of SEQ ID NO:1-3, substituted at positions 415, 420 and 421, respectively, in the amino acid sequence of SEQ ID NO:14;
- j) amino acid residues 234, 310, 316, 483 and 492 (Epitope F) of a norovirus strain having the amino acid sequence of any one of SEQ ID NO:1-3, substituted at positions 234, 324, 330, 492 and 501, respectively, in the amino acid sequence of SEQ ID NO:14, and
- k) amino acid residues 327 and 403 (Epitope Fs) of a norovirus strain having the amino acid sequence of any one of SEQ ID NO:1-3, substituted at positions 341 and 412, respectively, in the amino acid sequence of SEQ ID NO:14.
Dependencies are inferred from the claim text.