Patent
The present invention provides compositions useful to induce immune response to human metapneumovirus . Also provided are related materials and methods, including methods to induce an immune response in a mammal, comprising administering the compositions herein.
1. A composition comprising a live, attenuated human metapneumovirus (hMPV) comprising a mutated integrin-binding motif (RGD motif) in a fusion (F) protein of the live, attenuated hMPV, wherein the mutated RGD motif consists of a mutation or combination of mutations selected from: R329K; D331A; R329K and G330A; R329K and D331A; R329K and D331E; R329K and D331R; G330A and D331A; R329K, G330A, and D331A; R329K, G330A, and D331E; and R329K, G330A, and D331R.
2. The composition of claim 1 , wherein the mutated RGD motif consists of an R329K mutation, a D331A mutation, or both an R329K mutation and a D331A mutation.
3. The composition of claim 1 , wherein the mutated RGD motif consists of an R329K mutation.
4. The composition of claim 1 , wherein the mutated RGD motif consists of a D331A mutation.
5. The composition of claim 1 , wherein the composition is a pharmaceutical composition.
6. The composition of claim 1 , wherein the composition is a vaccine.
7. A method for inducing a protective immune response against human metapneumovirus (hMPV) or for treating hMPV infection in a mammal comprising administering to the mammal a pharmaceutically effective dose of the composition of claim 1 .
8. The method of claim 7 , wherein the composition is administered orally, subcutaneously, or intranasally.
9. The method of claim 7 , wherein the mammal is a human.
10. The method of claim 7 , further comprising administering at least one subsequent pharmaceutically effective dose of the composition to the mammal.
11. The method of claim 10 , wherein the at least one subsequent pharmaceutically effective dose is administered at a time interval selected from: approximately one week after the first dose; approximately two weeks after the first dose; approximately three weeks after the first dose; approximately four weeks after the first dose; approximately five weeks after the first dose; approximately six weeks after the first dose; approximately seven weeks after the first dose; and approximately eight weeks after the first dose.
12. A recombinant human metapneumovirus (hMPV) comprising a mutated integrin-binding motif (RGD motif) in a fusion (F) protein of the hMPV capable of inducing neutralizing antibody and a T cell immune response in a mammal without inducing clinical symptoms of hMPV infection, wherein the mutated RGD motif consists of a mutation or combination of mutations selected from R329K; D331A; R329K and G330A; R329K and D331A; R329K and D331E; R329K and D331R; G330A and D331A; R329K, G330A, and D331A; R329K, G330A, and D331E; and R329K, G330A, and D331R.
13. The recombinant hMPV of claim 12 , wherein the recombinant hMPV is selected from rhMPV-R329K; and rhMPV-D331A.
14. The recombinant hMPV of claim 12 , wherein the recombinant hMPV is rhMPV-R329K (SEQ ID NO: 2).
15. The recombinant hMPV of claim 12 , wherein the recombinant hMPV is rhMPV-D331A (SEQ ID NO: 4).
16. The composition of claim 6 , further comprising an adjuvant.
17. A method of preparing a pharmaceutical composition for inducing a protective immune response against human metapneumovirus (hMPV) in an individual in need thereof comprising mixing a composition of claim 1 with a suitable carrier, vehicle, and/or excipient.
18. The method according to claim 17 , wherein the pharmaceutical composition is formulated for oral, subcutaneous, or intranasal administration.
19. A method of attenuating a human metapneumovirus (hMPV) comprising mutating an integrin-binding motif (RGD motif) in a fusion (F) protein of the hMPV, wherein the RGD motif comprises an R329K mutation, or an R329K mutation and a D331A mutation.