Method of conferring a protective immune response to norovirus

Abstract

The present invention relates to vaccine compositions comprising Norovirus antigens and adjuvants, in particular, mixtures of monovalent VLPs and mixtures of multivalent VLPs, and to methods of conferring protective immunity to Norovirus infections in a human subject.

1 . A method of eliciting protective immunity to a  Norovirus  infection in a human comprising administering to the human a vaccine comprising  Norovirus  virus-like particles (VLPs) and at least one adjuvant. 
     
     
         2 . The method of  claim 1 , wherein said  Norovirus  VLPs are selected from the group consisting of  Norovirus  genogroup I and genogroup II viral strains. 
     
     
         3 . The method of  claim 1 , wherein said  Norovirus  VLPs are monovalent VLPs. 
     
     
         4 . The method of  claim 1 , wherein said  Norovirus  VLPs are multivalent VLPs. 
     
     
         5 . The method of  claim 1 , wherein said vaccine comprises a second type of  Norovirus  VLPs. 
     
     
         6 . The method of  claim 5 , wherein said first and second  Norovirus  VLPs are monovalent VLPs from different genogroups. 
     
     
         7 . The method of  claim 6 , wherein said first  Norovirus  VLPs are Norwalk virus VLPs and said second  Norovirus  VLPs are VLPs generated from expression of a consensus sequence of genogroup II  Norovirus.    
     
     
         8 . The method of  claim 1 , wherein said vaccine further comprises a delivery agent. 
     
     
         9 . The method of  claim 8 , wherein the delivery agent is a bioadhesive. 
     
     
         10 . The method of  claim 9 , wherein said bioadhesive is a mucoadhesive. 
     
     
         11 . The method of  claim 10 , wherein said mucoadhesive is selected from the group consisting of dermatan sulfate, chondroitin, pectin, mucin, alginate, cross-linked derivatives of poly(acrylic acid), polyvinyl alcohol, polyvinyl pyrollidone, polysaccharides, hydroxypropyl methylcellulose, lectins, fimbrial proteins, and carboxymethylcellulose. 
     
     
         12 . The method of  claim 11 , wherein said mucoadhesive is a polysaccharide. 
     
     
         13 . The method of  claim 12 , wherein said polysaccharide is chitosan, chitosan salt, or chitosan base. 
     
     
         14 . The method of  claim 1 , wherein the adjuvant is selected from the group consisting of toll-like receptor (TLR) agonists, monophosphoryl lipid A (MPL), synthetic lipid A, lipid A mimetics or analogs, aluminum salts, cytokines, saponins, muramyl dipeptide (MDP) derivatives, CpG oligos, lipopolysaccharide (LPS) of gram-negative bacteria, polyphosphazenes, emulsions, virosomes, cochleates, poly(lactide-co-glycolides) (PLG) microparticles, poloxamer particles, microparticles, liposomes, oil-in-water emulsion, MF59, and squalene. 
     
     
         15 . The method of  claim 14 , wherein the adjuvant is a toll-like receptor (TLR) agonist. 
     
     
         16 . The method of  claim 14 , wherein the adjuvant is MPL. 
     
     
         17 . The method of  claim 1 , wherein the vaccine comprises two adjuvants. 
     
     
         18 . The method of  claim 17 , wherein the two adjuvants are MPL and alum. 
     
     
         19 . The method of  claim 1 , wherein the adjuvant is not a toxin adjuvant. 
     
     
         20 . The method of  claim 1 , wherein the vaccine is in a powder formulation. 
     
     
         21 . The method of  claim 1 , wherein the vaccine is in a liquid formulation. 
     
     
         22 . The method of  claim 1 , wherein said vaccine is administered to the human by a route selected from the group consisting of mucosal, intranasal, parenteral, intramuscular, intravenous, subcutaneous, intradermal, subdermal, and transdermal routes of administration. 
     
     
         23 . The method of  claim 22 , wherein said vaccine is administered intranasally. 
     
     
         24 . The method of  claim 23 , wherein the administration of the vaccine elicits a protective immunity comprising an increase in the serum titer of  Norovirus -specific functional antibodies as compared to the serum titer in a human not receiving the vaccine. 
     
     
         25 . The method of  claim 24 , wherein the serum titer of  Norovirus -specific functional antibodies is a geometric mean titer greater than 40 titer/mL as measured by a hemagglutination inhibition assay. 
     
     
         26 . The method of  claim 23 , wherein the administration of the vaccine elicits a protective immunity comprising an increase in the level of IgA  Norovirus -specific antibody secreting cells in the blood as compared to the level in a human not receiving the vaccine. 
     
     
         27 . The method of  claim 26 , wherein the IgA  Norovirus -specific antibody secreting cells are CD19+, CD27+, CD62L+, and α4β7+. 
     
     
         28 . The method of  claim 23 , wherein said vaccine is administered to the nasal mucosa by rapid deposition within the nasal passage from one or more devices comprising the vaccine held close to the nasal passageway. 
     
     
         29 . The method of  claim 28 , wherein said vaccine is administered to one or both nostrils. 
     
     
         30 . The method of  claim 22 , wherein said vaccine is administered intramuscularly. 
     
     
         31 . The method of  claim 30 , wherein the administration of the vaccine elicits a protective immunity comprising an increase in the serum titer of  Norovirus -specific functional antibodies as compared to the serum titer in a human not receiving the vaccine. 
     
     
         32 . The method of  claim 31 , wherein the serum titer of  Norovirus -specific functional antibodies is a geometric mean titer greater than 40 titer/mL as measured by a hemagglutination inhibition assay. 
     
     
         33 . The method of  claim 1 , wherein the  Norovirus  VLPs are present in a concentration of from about 0.01% (w/w) to about 80% (w/w). 
     
     
         34 . The method of  claim 1 , wherein the  Norovirus  VLPs are present in an amount of from about 1 μg to about 100 mg per dose. 
     
     
         35 . The method of  claim 34 , wherein the  Norovirus  VLPs are present from about 1 μg to about 200 μg per dose. 
     
     
         36 . The method of  claim 35 , wherein the  Norovirus  VLPs are present at about 50 μg per dose. 
     
     
         37 . The method of  claim 35 , wherein the  Norovirus  VLPs are present at about 100 μg per dose. 
     
     
         38 . The method of  claim 35 , wherein the  Norovirus  VLPs are present at about 150 μg per dose. 
     
     
         39 . The method of  claim 1 , wherein said vaccine confers protection from one or more symptoms of  Norovirus  infection.