METHOD OF CONFERRING A PROTECTIVE IMMUNE RESPONSE TO NOROVIRUS
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.