Norovirus and sapovirus antigens

Abstract

Immunogenic compositions that elicit immune responses against Norovirus and Sapovirus antigens are described. In particular, the invention relates to polynucleotides encoding one or more capsid proteins or other immunogenic viral polypeptides from one or more strains of Norovirus and/or Sapovirus , coexpression of such immunogenic viral polypeptides with adjuvants, and methods of using the polynucleotides in applications including immunization and production of immunogenic viral polypeptides and viral-like particles (VLPs). Methods for producing Norovirus - or Sapovirus -derived multiple epitope fusion antigens or polyproteins and immunogenic compositions comprising one or more immunogenic polypeptides, polynucleotides, VLPs, and/or adjuvants are also described. The immunogenic compositions of the invention may also contain antigens other than Norovirus or Sapovirus antigens, including antigens that can be used in immunization against pathogens that cause diarrheal diseases, such as antigens derived from rotavirus.

1 . A recombinant polynucleotide comprising a nucleotide sequence with at least 98% sequence identity to the nucleotide sequence of SEQ ID NO:1. 
     
     
         2 . The recombinant polynucleotide of  claim 1 , wherein the polynucleotide comprises the nucleotide sequence of SEQ ID NO:1. 
     
     
         3 . A recombinant polynucleotide comprising nucleotides 692-1608 of SEQ ID NO:1. 
     
     
         4 . The recombinant polynucleotide of  claim 3  consisting of nucleotides 692-1608 of SEQ ID NO:1. 
     
     
         5 . A recombinant vector comprising the polynucleotide of  claim 1  operably linked to control elements that direct the expression of said nucleotide sequence in a host cell. 
     
     
         6 . A recombinant vector comprising the polynucleotide of  claim 3  operably linked to control elements that direct the expression of said nucleotide sequence in a host cell. 
     
     
         7 . The recombinant vector of  claim 5 , wherein the nucleotide sequence is operably linked to an ADH2 promoter. 
     
     
         8 . The recombinant vector of  claim 6 , wherein the nucleotide sequence is operably linked to an ADH2 promoter 
     
     
         9 . The recombinant vector of  claim 7 , wherein the nucleotide sequence is operably linked to a hybrid ADH2/GAPDH promoter. 
     
     
         10 . The recombinant vector of  claim 8 , wherein the nucleotide sequence is operably linked to a hybrid ADH2/GAPDH promoter. 
     
     
         11 . The recombinant vector of  claim 9 , further comprising an alpha-factor terminator. 
     
     
         12 . The recombinant vector of  claim 10 , further comprising an alpha-factor terminator. 
     
     
         13 . An isolated cell comprising the recombinant vector of  claim 5 . 
     
     
         14 . An isolated cell comprising the recombinant vector of  claim 6 . 
     
     
         15 . An isolated cell comprising the recombinant vector of  claim 7 . 
     
     
         16 . An isolated cell comprising the recombinant vector of  claim 8 . 
     
     
         17 . The cell of  claim 15 , wherein the cell is a yeast cell. 
     
     
         18 . The cell of  claim 16 , wherein the cell is a yeast cell. 
     
     
         19 . A method of producing a recombinant polypeptide comprising:
 (a) providing a population of host cells according to  claim 13 ; and   (b) culturing said population of cells under conditions whereby a polypeptide encoded by the nucleic acid sequence present in said recombinant vector is expressed.   
     
     
         20 . A method of producing a recombinant polypeptide comprising:
 (a) providing a population of host cells according to  claim 14 ; and   (b) culturing said population of cells under conditions whereby a polypeptide encoded by the nucleic acid sequence present in said recombinant vector is expressed.   
     
     
         21 . A composition comprising the recombinant polynucleotide of  claim 1  and a pharmaceutically acceptable excipient. 
     
     
         22 . A composition comprising the recombinant polynucleotide of  claim 3  and a pharmaceutically acceptable excipient.