Norovirus S particle based vaccines and methods of making and using same

1. A polyvalent icosahedral composition for antigen presentation comprising an S particle, wherein said S particle comprises a recombinant fusion protein comprising

a) a norovirus (NoV) S domain protein comprising a mutation at position 69, and a mutation selected from 57C/140C, 57C/58C/136C, and 57C/58C/136C/140C;

b) a linker protein domain operatively connected to said norovirus S domain protein; and

c) an antigen protein domain operatively connected to said linker;

wherein said mutations are with reference to SEQ ID NO: 25;

wherein said mutation at position 69 renders a cleavage site between R69 and N70 resistant to trypsin cleavage; and

wherein said norovirus is a human calicivirus.

2. The polyvalent icosahedral composition of claim 1 , wherein said composition has an icosahedral symmetry structure.

3. The polyvalent icosahedral composition of claim 1 , wherein said composition comprises 60 sites for antigen presentation.

4. The polyvalent icosahedral composition of claim 1 , wherein said norovirus S domain protein comprises a mutation sufficient to provide a non-native disulfide bond binding site.

5. The polyvalent icosahedral composition of claim 1 , wherein said norovirus S domain protein comprises a mutation of at least two amino acids sufficient to provide at least one non-native disulfide bond binding site, or at least two non-native disulfide bond binding sites, or at least three non-native disulfide bond binding sites between neighboring S domain proteins of the polyvalent icosahedral S particle.

6. The polyvalent icosahedral composition of claim 1 , wherein said calicivirus has 180 copies of a single capsid protein.

7. The polyvalent icosahedral composition of claim 1 , wherein said linker comprises three to six amino acids.

8. The polyvalent icosahedral composition of claim 1 , wherein said antigen protein domain comprises an antigen having a size of from 8 amino acids up to about 300 amino acids, or from 8 amino acids up to about 400 amino acids, or from 8 amino acids up to about 500 amino acids.

9. The polyvalent icosahedral composition of claim 1 , wherein said antigen protein domain comprises a rotavirus (RV) antigen.

10. The polyvalent icosahedral composition of claim 1 , wherein said antigen protein domain comprises an RV spike protein antigen (VP8 antigen).

11. The polyvalent icosahedral composition of claim 1 , wherein said antigen protein domain comprises an antigen selected from a TSR antigen of circumsporozoite protein (CSP) of malaria parasite Plasmodium falciparum, a receptor-binding domain of the HA1 protein and an M2e epitope of influenza A virus, a P domain antigen of hepatitis E, a surface spike protein of the astrovirus, and combinations thereof.

12. A recombinant fusion protein comprising

a) a norovirus (NoV) S domain protein comprising a mutation at position 69, and a mutation selected from 57C/140C, 57C/58C/136C, and 57C/58C/136C/140C;

b) a linker protein domain operatively connected to said norovirus S domain protein; and

c) an antigen protein domain operatively connected to said linker;

wherein said mutation at position 69 renders a cleavage site between R69 and N70 resistant to trypsin cleavage;

wherein said mutations are with reference to SEQ ID NO: 25; and

wherein said norovirus is a human calicivirus.

13. A method of making the polyvalent icosahedral structure of claim 1 , comprising the steps of a) making a first region comprising a norovirus (NoV) S domain protein comprising a mutation at position 69, and a mutation selected from 57C/140C, 57C/58C/136C, and 57C/58C/136C/140C and b) recombinantly expressing said first region with a linker and an antigen, wherein said mutations are with reference to SEQ ID NO: 25.

14. The method of claim 13 , wherein said composition is produced in E.coli.

15. A method of eliciting an immune response in an individual in need thereof, comprising the step of administering a composition according to claim 1 .

16. A container comprising at least one dose of composition according to claim 1 .

17. A kit comprising one or more containers according to claim 16 , a delivery device, and instructions for administration of said composition.

18. The composition of claim 1 wherein said mutation at position 69 is an R69A mutation.