Metapneumovirus immunogens and related materials and methods

Patent metadata

Field	Value
Publication number	US-10093702-B2
Application number	US-201414777095-A
Country	US
Kind code	B2
Filing date	Mar 14, 2014
Priority date	Mar 15, 2013
Publication date	Oct 9, 2018
Grant date	Oct 9, 2018

Abstract

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.

First claim

The invention claimed is:

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.

Assignees

• Res Inst Nationwide Childrens Hospital
• Ohio State Innovation Foundation

Inventors

• Li Jianrong
• Wei Yongwei
• Zhang Yu
• Peeples Mark E

Classifications

• A61K39/155 Primary

  Paramyxoviridae, e.g. parainfluenza virus · CPC title

• C12N2760/18334

  Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein · CPC title

• A61K2039/5254

  avirulent or attenuated · CPC title

• C07K14/005 Primary

  from viruses · CPC title

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title