Nanoparticle vaccines with novel structural components

Patent metadata

Field	Value
Publication number	US-11097002-B2
Application number	US-201916440067-A
Country	US
Kind code	B2
Filing date	Jun 13, 2019
Priority date	Jun 13, 2018
Publication date	Aug 24, 2021
Grant date	Aug 24, 2021

Abstract

The present invention provides novel nanoparticle presented vaccine compositions that are stabilized with a locking domain. Various immunogens can be employed in the preparation of the vaccine compositions, including viral immunogens such as HIV-1 and Ebola viral immunogens, and non-viral immunogens such as immunogens derived from bacteria, parasites and mammalian species. The invention also provides methods of using such vaccine compositions in various therapeutic applications, e.g., for preventing or treating viral infections.

First claim

What is claimed is:

1. A vaccine composition, comprising a polypeptide immunogen that is displayed on the surface of a self-assembling nanoparticle, wherein a locking domain is embedded inside the self-assembling nanoparticle and is linked to a subunit of the self-assembling nanoparticle, and wherein the locking domain comprises the amino acid sequence selected from SEQ ID NOs:1-9, or a conservatively modified variant thereof.

2. The vaccine composition of claim 1 , wherein the locking domain is covalently linked to a subunit of the self-assembling nanoparticle.

3. The vaccine composition of claim 2 , wherein N-terminus of the locking domain is fused to C-terminus of the self-assembling nanoparticle subunit via a linker sequence.

4. The vaccine composition of claim 1 , further comprising a pan-reactive T-cell epitope.

5. The vaccine composition of claim 4 , wherein N-terminus of the pan-reactive T-cell epitope is fused to the C-terminus of the locking domain.

6. The vaccine composition of claim 1 , further comprising a neck region inserted between the immunogen and the self-assembling nanoparticle subunit, wherein the neck region comprises a 3-helix protein domain that elevates the immunogen further away from the surface of the self-assembling nanoparticle.

7. The vaccine composition of claim 1 , further comprising a protein domain inserted between the immunogen and the self-assembling nanoparticle subunit, wherein the protein domain stabilizes the immunogen polypeptide.

8. The vaccine composition of claim 1 , wherein the self-assembling nanoparticle is a ball-shaped nanoparticle with rotational symmetry.

9. The vaccine composition of claim 8 , wherein the rotational symmetry has 3-fold axis and/or 5-fold axis.

10. The vaccine composition of claim 9 , wherein the nanoparticle is of an icosahedral structure.

11. The vaccine composition of claim 1 , wherein the polypeptide immunogen is a viral immunogen.

12. The vaccine composition of claim 11 , wherein the polypeptide immunogen is a viral immunogen from a virus utilizing class-I fusion mechanism.

13. The vaccine composition of claim 12 , wherein the virus is selected from the group consisting of HIV-1 virus, Ebola virus, Marburg virus, Arenaviruses, respiratory syncytial viruses (RSV), and coronaviruses.

14. The vaccine composition of claim 11 , wherein the polypeptide immunogen is a viral immunogen from a virus utilizing class-II fusion mechanism.

15. The vaccine composition of claim 14 , wherein the virus utilizing class-II fusion mechanism is HCV or Zika virus.

16. The vaccine composition of claim 11 , wherein the polypeptide immunogen is a non-viral immunogen.

17. The vaccine composition of claim 16 , wherein the polypeptide immunogen is an antigen from Plasmodium falciparum , an antigen from Mycobacterium tuberculosis (TB), or human protein proprotein convertase subtilisin/kexin type 9 (PCSK9).

18. The vaccine composition of claim 1 , wherein the polypeptide immunogen is an HIV-1 Env trimer protein.

19. The vaccine composition of claim 18 , wherein N-terminus of the locking domain is fused to C-terminus of the nanoparticle subunit via a linker sequence that comprises one or more tandem copies of GGGGS (SEQ ID NO:17).

20. The vaccine composition of claim 18 , further comprising a pan-reactive T-cell epitope.

21. The vaccine composition of claim 20 , wherein N-terminus of the pan-reactive T-cell epitope is fused to the C-terminus of the locking domain.

22. The vaccine composition of claim 20 , wherein the pan-reactive T-cell epitope comprises the sequence AKFVAAWTLKAAA (SEQ ID NO:18).

23. The vaccine composition of claim 18 , wherein C-terminus of subunit of the HIV-1 trimer protein is covalently linked to N-terminus of subunit of the self-assembling nanoparticle.

24. The vaccine composition of claim 18 , wherein the HIV-1 trimer protein subunit is fused to the self-assembling nanoparticle subunit via a linker sequence.

25. The vaccine composition of claim 24 , wherein the linker sequence comprises the sequence (GaSb)n, wherein a is an integer of 1 to 5, b is an integer of 1 to 2, and n is an integer of 1 to 5.

26. The vaccine composition of claim 18 , wherein the self-assembling nanoparticle comprises a trimeric sequence.

27. The vaccine composition of claim 18 , wherein the subunit of the self-assembling nanoparticle comprises the polypeptide selected from SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:25 or SEQ ID NO:26, or a conservatively modified variant thereof.

28. The vaccine composition of claim 18 , wherein the HIV-1 Env trimer protein is a gp140 trimer.

29. The vaccine composition of claim 18 , wherein the HIV-1 Env trimer protein is an uncleaved prefusion-optimized (UFO) gp140 trimer.

30. The vaccine composition of claim 29 , wherein the UFO gp140 trimer is a chimeric trimer comprising a modified gp4lEcTo domain from HIV-1 strain BG505.

31. The vaccine composition of claim 29 , wherein subunit of the UFO gp140 trimer comprises the sequence SEQ ID NO:23, or a conservatively modified variant thereof.

32. The vaccine composition of claim 29 , having a subunit sequence that comprises from the N-terminus to the C-terminus: HIV-1 uncleaved prefusion-optimized (UFO) gp140 trimer subunit comprising SEQ ID NO:23, self-assembling nanoparticle subunit comprising SEQ ID NO:21 (E2p), the locking domain comprising SEQ ID NO:1 (LD4), and T-cell epitope AKFVAAWTLKAAA (SEQ ID NO:18).

33. The vaccine composition of claim 32 , further comprising a first linker sequence (GGGGS)2 (SEQ ID NO:24) between the HIV-1 uncleaved prefusion-optimized (UFO) gp140 trimer subunit and the self-assembling nanoparticle subunit, and/or a second linker sequence GGGGS (SEQ ID NO:17) between the self-assembling nanoparticle subunit and the locking domain.

34. The vaccine composition of claim 29 , having a subunit sequence that comprises from the N-terminus to the C-terminus: HIV-1 uncleaved prefusion-optimized (UFO) gp140 trimer comprising SEQ ID NO:23, self-assembling nanoparticle subunit comprising SEQ ID NO:22 or 25 (13-01), the locking domain comprising SEQ ID NO:2 (LD7), and T-cell epitope AKFVAAWTLKAAA (SEQ ID NO:18).

35. The vaccine composition of claim 34 , further comprising a first linker sequence (GGGGS)2 (SEQ ID NO:24) between the HIV-1 uncleaved prefusion-optimized (UFO) gp140 trimer subunit and the self-assembling nanoparticle subunit, and/or a second linker sequence GGGGS (SEQ ID NO:17) between the self-assembling nanoparticle subunit and the locking domain.

36. A pharmaceutical composition, comprising the vaccine composition of claim 1 , and a pharmaceutically acceptable carrier.

Assignees

• Scripps Research Inst

Inventors

• He Linling
• Zhu Jiang

Classifications

• B82Y40/00

  Manufacture or treatment of nanostructures · CPC title

• B82Y30/00

  Nanotechnology for materials or surface science, e.g. nanocomposites · CPC title

• A61K2039/60

  characteristics by the carrier linked to the antigen · CPC title

• A61K2039/6031

  Proteins · CPC title

• A61K39/21 Primary

  Retroviridae, e.g. equine infectious anemia virus · CPC title