Vaccine compositions having improved stability and immunogenicity

Patent metadata

Field	Value
Publication number	US-12257297-B2
Application number	US-202217750612-A
Country	US
Kind code	B2
Filing date	May 23, 2022
Priority date	Sep 3, 2015
Publication date	Mar 25, 2025
Grant date	Mar 25, 2025

Abstract

Disclosed herein are nanoparticles suitable for use in vaccines. The nanoparticles present antigens from pathogens surrounded to and associated with a detergent core resulting in enhanced stability and good immunogenicity. Dosages, formulations, and methods for preparing the vaccines and nanoparticles are also disclosed.

First claim

The invention claimed is:

1. A nanoparticle comprising: an Ebola virus glycoprotein (GP) and a non-ionic detergent core;
wherein the GP comprises a GP1 domain and a GP2 domain;
wherein the GP1 domain and GP2 domain are connected via a disulfide bond;
wherein the GP2 polypeptide is associated with the non-ionic detergent core and the GP1 polypeptide extends outward; and
wherein the GP is a trimer.

2. The nanoparticle of claim 1 , wherein the GP comprises the polypeptide sequence of SEQ ID NO: 29.

3. The nanoparticle of claim 1 , wherein the GP is isolated from a Makona, Sudan, Zaire, or Reston Ebola virus strain.

4. The nanoparticle of claim 1 , wherein the GP is at least 80% identical to SEQ ID NO:29.

5. The nanoparticle of claim 1 , wherein the non-ionic detergent is selected from the group consisting of PS20, PS40, PS60, PS65, and PS80.

6. The nanoparticle of claim 1 , wherein the non-ionic detergent is PS80.

7. The nanoparticle of claim 1 , wherein the GP is expressed in an insect cell.

8. The nanoparticle of claim 7 , wherein the insect cell is a Spodoptera frugiperda Sf9 cell.

9. An immunogenic composition, comprising:
(i) the nanoparticle of claim 1 ;
(ii) a saponin adjuvant; and
(iii) a pharmaceutically acceptable buffer.

10. The immunogenic composition of claim 9 , wherein the GP of the nanoparticle comprises the polypeptide sequence of SEQ ID NO: 29.

11. The immunogenic composition of claim 9 , wherein the GP of the nanoparticle is isolated from a Makona, Sudan, Zaire, or Reston Ebola virus strain.

12. The immunogenic composition of claim 9 , wherein the GP of the nanoparticle is at least 80% identical to SEQ ID NO:29.

13. The immunogenic composition of claim 9 , wherein the non-ionic detergent of the nanoparticle is selected from the group consisting of PS20, PS40, PS60, PS65, and PS80.

14. The immunogenic composition of claim 9 , wherein the non-ionic detergent of the nanoparticle is PS80.

15. The immunogenic composition of claim 9 , wherein the GP of the nanoparticle is expressed in an insect cell.

16. The immunogenic composition of claim 15 , wherein the insect cell is a Spodoptera frugiperda Sf9 cell.

17. The immunogenic composition of claim 9 , wherein the saponin adjuvant comprises at least two iscom particles;
wherein the first iscom particle comprises fraction A of Quillaja saponaria Molina and not fraction C of Quillaja saponaria Molina; and
wherein the second iscom particle comprises fraction C of Quillaja saponaria Molina and not fraction A of Quillaja saponaria Molina.

18. The immunogenic composition of claim 17 , wherein fraction A of Quillaja saponaria Molina accounts for 50-99% by weight and fraction C of Quillaja saponaria Molina accounts for the remainder, respectively, of the sum of the weights of fraction A of Quillaja saponaria Molina and fraction C of Quillaja saponaria Molina in the adjuvant.

19. The immunogenic composition of claim 17 , wherein fraction A of Quillaja saponaria Molina and fraction C of Quillaja saponaria Molina account for about 85% by weight and about 15% by weight, respectively, of the sum of the weights of fraction A of Quillaja saponaria Molina and fraction C of Quillaja saponaria Molina in the adjuvant.

20. A method of stimulating an immune response against Ebola virus in a subject comprising administering the immunogenic composition of claim 9 .

21. The method of claim 20 , wherein the GP of the nanoparticle of the immunogenic composition comprises the polypeptide sequence of SEQ ID NO: 29.

22. The method of claim 20 , wherein the GP of the nanoparticle of the immunogenic composition is isolated from a Makona, Sudan, Zaire, or Reston Ebola virus strain.

23. The method of claim 20 , wherein the GP of the nanoparticle of the immunogenic composition is at least 80% identical to SEQ ID NO:29.

24. The method of claim 20 , wherein the non-ionic detergent of the nanoparticle of the immunogenic composition is selected from the group consisting of PS20, PS40, PS60, PS65, and PS80.

25. The method of claim 20 , wherein the non-ionic detergent of the nanoparticle of the immunogenic composition is PS80.

26. The method of claim 20 , wherein the GP of the nanoparticle of the immunogenic composition is expressed in an insect cell.

27. The method of claim 26 , wherein the insect cell is a Spodoptera frugiperda Sf9 cell.

28. The method of claim 20 , wherein the saponin adjuvant of the immunogenic composition comprises at least two iscom particles;
wherein the first iscom particle comprises fraction A of Quillaja saponaria Molina and not fraction C of Quillaja saponaria Molina; and
wherein the second iscom particle comprises fraction C of Quillaja saponaria Molina and not fraction A of Quillaja saponaria Molina.

29. The method of claim 28 , wherein fraction A of Quillaja saponaria Molina accounts for 50-99% by weight and fraction C of Quillaja saponaria Molina accounts for the remainder, respectively, of the sum of the weights of fraction A of Quillaja saponaria Molina and fraction C of Quillaja saponaria Molina in the adjuvant.

30. The method of claim 28 , wherein fraction A of Quillaja saponaria Molina and fraction C of Quillaja saponaria Molina account for about 85% by weight and about 15% by weight, respectively, of the sum of the weights of fraction A of Quillaja saponaria Molina and fraction C of Quillaja saponaria Molina in the adjuvant.

Assignees

• Novavax Inc

Inventors

• Smith Gale
• Liu Ye
• Tian Jing-Hui
• Massare Michael J
• Boddapati Sarathi
• Shane Erica
• Oliver Cynthia
• Glenn Gregory

Classifications

• C12N7/00

  Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00) · CPC title

• C12N2760/16222

  New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes · CPC title

• A61P31/14

  for RNA viruses · CPC title

• A61K9/0019 Primary

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• A61K2039/55505

  Inorganic adjuvants · CPC title