Granted Patent
B2
US 12,257,297 · App. 17/750,612 · Granted Mar 25, 2025
Vaccine compositions having improved stability and immunogenicity
Inventors:
Gale Smith (Germantown, MD); Ye Liu (Clarksville, MD); Jing-Hui Tian (Germantown, MD); Michael J. Massare (Mt. Airy, MD); Sarathi Boddapati (Germantown, MD); Erica Shane (McLean, VA); Cynthia Oliver (Potomac, MD); Gregory Glenn (Poolesville, MD)
A61K39/155A61K9/0019A61K9/1611A61K9/1617A61K39/12C12N7/00A61K2039/54A61K2039/55505A61K2039/55555C12N2710/14143C12N2760/14134C12N2760/14171C12N2760/16122C12N2760/16134C12N2760/16151C12N2760/16222C12N2760/16234C12N2760/16251C12N2760/18522C12N2760/18534
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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.
Claims (41)
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.
Assignments (2)
SECURITY INTEREST
Recorded Feb 25, 2026
From: NOVAVAX, INC.
To: MIDCAP FINANCIAL TRUST
Reel/Frame 074976/0089 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded May 24, 2022
From: SMITH, GALE; LIU, YE; TIAN, JING-HUI; MASSARE, MICHAEL J.; BODDAPATI, SARATHI; SHANE, ERICA; OLIVER, CYNTHIA; GLENN, GREGORY
To: NOVAVAX, INC.
Reel/Frame 059994/0494 →
Continuity (7)
Provisional Application
62350973
· Jun 16, 2016
Provisional Application
62309216
· Mar 16, 2016
Provisional Application
62255786
· Nov 16, 2015
Provisional Application
62213947
· Sep 3, 2015
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