Norovirus vaccine

Abstract

A dry powder norovirus vaccine is provided, which comprises at least two norovirus antigens representing different genogroups. The vaccine may be produced by formulation with a mixture of different antigens or combination of monovalent powders with each containing one antigen. The formulated vaccine is suitable for mucosal administration and soluble in aqueous solutions for parenteral administration. A method of immunization is also provided, which comprises at least one administration of the vaccine via mucosal and/or parental route. The immunization may have multiple administrations of the vaccine, i.e., one or more immunizations via a mucosal route followed by one or more immunizations via a parenteral route or vice versa, to maximize both mucosal and systemic immune responses and protection against norovirus infections.

We claim: 
     
         1 - 47 . (canceled) 
     
     
         48 . A multivalent norovirus dry powder vaccine composition comprising:
 a first norovirus virus-like particle (VLP) antigen of GI genotype;   a second norovirus VLP antigen of GII genotype; and   an anionic polysaccharide.   
     
     
         49 . The composition of  claim 48 , wherein the multivalent norovirus dry powder vaccine composition is suitable for both parenteral and mucosal routes of administration. 
     
     
         50 . The composition of  claim 48 , wherein the amount of norovirus VLP antigen of GI genotype is about 10 μg to 50 μg per 20 mg dry powder vaccine composition. 
     
     
         51 . The composition of  claim 48 , wherein the amount of norovirus VLP antigen of GII genotype is about 10 μg to 50 μg per 20 mg dry powder composition. 
     
     
         52 . The composition of  claim 48 , wherein the anionic polysaccharide is in the amount of about 0.25% of the composition. 
     
     
         53 . The composition of  claim 48 , wherein the mean microparticle diameter of the dry powder vaccine composition is 24 μm to 37 μm. 
     
     
         54 . The composition of  claim 48 , wherein the anionic polysaccharide is sodium polygalacturonate. 
     
     
         55 . The composition of  claim 48 , wherein the amount of norovirus VLP antigen of GI genotype and the amount of norovirus VLP antigen of GII genotype are in a proportion in the range of 1:1 to 3:1. 
     
     
         56 . A method of immunizing a mammalian subject against a norovirus infection with a multivalent norovirus dry powder vaccine composition comprising a norovirus VLP antigen of GI genotype, a norovirus VLP antigen of GII genotype, and an ionic polysaccharide, the method comprising:
 administering to the subject at least one dose of the vaccine composition, thereby initiating an immune response against a norovirus antigen sufficient to confer active immunity against a norovirus infection in the subject.   
     
     
         57 . The method of  claim 56 , wherein the vaccine composition is administered by mucosal route and/or parental route. 
     
     
         58 . The method of  claim 56 , further comprising reconstituting the vaccine composition in aqueous solution, wherein the vaccine composition is administered by a parenteral route. 
     
     
         59 . The method of  claim 56 , wherein at least 20 mg of the vaccine composition is administered by the mucosal route. 
     
     
         60 . The method of  claim 56 , wherein at least 5 μg of the norovirus VLP antigen of GI genotype and at least 5 μg of norovirus VLP antigen of GII genotype is administered in each dose. 
     
     
         61 . The method of  claim 57 , wherein the total dose per subject administered by mucosal route and/or parental route is at least 50 μg of norovirus VLP antigen of GI genotype and at least 50 μg of norovirus VLP antigen of GII genotype. 
     
     
         62 . A method for producing a multivalent dry powder norovirus vaccine composition suitable for both parenteral and mucosal routes of administration comprising:
 a. obtaining a first solution comprising a norovirus virus-like particle (VLP) antigen of GI genotype;   b. introducing to the first solution, an anionic polysaccharide;   c. drying the first solution with the anionic polysaccharide to a substantially non-aqueous state, thereby producing a first dry powder formulation;   d. obtaining a second solution comprising a norovirus VLP antigen of GII genotype;   e. introducing to the second solution an anionic polysaccharide;   f. drying the second solution with the anionic polysaccharide to a substantially non-aqueous state, thereby producing a second dry powder formulation;   g. combining the first and second dry powder formulations to form a multivalent dry powder norovirus vaccine formulation.   
     
     
         63 . The method of  claim 62 , wherein the drying is by lyophilization. 
     
     
         64 . The method of  claim 62 , wherein the drying is by spray drying. 
     
     
         65 . The method of  claim 62 , wherein the norovirus VLP of GI genotype and norovirus VLP of GII genotype are obtained by expressing the recombinant virus-like particles in an expression system selected from the group consisting of: prokaryote cells, eukaryote cells,  E. coli  cells,  S. cerevisiae  cells, insect cells, mammalian cells, HEK293 cells, CHO cells, tobacco mosaic virus, and baculovirus.