IP Library › Granted Patent US 12,447,206
Granted Patent B2
US 12,447,206 · App. 17/386,289 · Granted Oct 21, 2025

Nanoparticle vaccines with novel structural components

Inventors: Linling He (San Diego, CA); Jiang Zhu (San Diego, CA)
Assignee: The Scripps Research Institute
A61K39/21A61K47/6425A61K47/6929A61P31/18C12N15/86B82Y5/00B82Y30/00B82Y40/00
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Quick Facts
Patent No.
US 12,447,206
App. No.
17/386,289
Granted
Oct 21, 2025
Kind
B2
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.

Claims (35)

1. A polynucleotide, encoding a fusion protein comprising (a) an polypeptide immunogen, (b) a self-assembling nanoparticle subunit, and (c) a locking domain subunit that comprises the amino acid sequence set forth in SEQ ID NO:2, or a conservatively modified variant thereof.

2. The polynucleotide of claim 1 , wherein the polypeptide immunogen is located at the N-terminus of the fusion protein.

3. The polynucleotide of claim 1 , wherein N-terminus of the locking domain subunit is fused to C-terminus of the self-assembling nanoparticle subunit via a linker sequence.

4. The polynucleotide of claim 1 , wherein the fusion protein further comprises a pan-reactive T-cell epitope.

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

6. The polynucleotide of claim 1 , wherein the fusion protein further comprises 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 from the surface of the self-assembling nanoparticle.

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

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

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

10. The polynucleotide of claim 9 , wherein the nanoparticle has an icosahedral structure.

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

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

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

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

16. The polynucleotide of claim 1 , wherein the polypeptide immunogen is a non-viral immunogen.

17. The polynucleotide 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 polynucleotide of claim 1 , wherein the polypeptide immunogen is an HIV-1 Env trimer protein.

19. The polynucleotide of claim 18 , wherein N-terminus of the locking domain subunit 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 polynucleotide of claim 18 , wherein the fusion protein further comprises a pan-reactive T-cell epitope.

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

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

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

25. The polynucleotide 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 polynucleotide of claim 18 , wherein the self-assembling nanoparticle comprises a trimeric sequence.

27. The polynucleotide 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 polynucleotide of claim 18 , wherein the HIV-1 Env trimer protein is a gp140 trimer.

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

30. The polynucleotide of claim 29 , wherein the UFO gp140 trimer is a chimeric trimer comprising a modified gp41 ECTO domain from HIV-1 strain BG505.

31. The polynucleotide 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 polynucleotide of claim 29 , wherein the fusion protein 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 (I3-01), said locking domain subunit, and T-cell epitope AKFVAAWTLKAAA (SEQ ID NO:18).

33. The polynucleotide of claim 32 , wherein the fusion protein further comprises 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 subunit.

34. A vector comprising the polynucleotide of claim 1 .

35. A pharmaceutical composition, comprising the polynucleotide of claim 1 , and a pharmaceutically acceptable carrier.

Continuity (3)
Division 16440067 · Jun 13, 2019
Provisional Application 62684229 · Jun 13, 2018
Related Publication 20220031835A1 · Feb 3, 2022
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