Vaccine compositions having improved stability and immunogenicity

Patent metadata

Field	Value
Publication number	US-11253585-B2
Application number	US-201916545424-A
Country	US
Kind code	B2
Filing date	Aug 20, 2019
Priority date	Sep 3, 2015
Publication date	Feb 22, 2022
Grant date	Feb 22, 2022

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 method of stimulating an immune response in a subject comprising administering a vaccine composition comprising:
(i) a nanoparticle comprising a non-ionic detergent core and a viral glycoprotein, wherein the viral glycoprotein is associated with the core; wherein the non-ionic detergent is PS80; wherein the viral glycoprotein is an RSV F glycoprotein and the molar ratio of PS80 to viral glycoprotein is about 30:1 to about 60:1; and
(ii) a pharmaceutically acceptable buffer.

2. The method of claim 1 , wherein the vaccine composition is administered intramuscularly.

3. The method of claim 1 , wherein a single dose of the vaccine composition is administered.

4. The method of claim 1 , wherein multiple doses of the vaccine composition are administered.

5. The method of claim 1 , wherein a dose of the vaccine composition comprises between about 30 μg and about 150 μg of the RSV F glycoprotein.

6. The method of claim 1 , wherein the subject is selected from the group consisting of an adult, a senior adult, a pregnant female adult, a child, a neonate, and an infant.

7. The method of claim 1 , wherein the composition comprises an adjuvant.

8. The method of claim 7 , wherein the 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 the second iscom particle comprises fraction C of Quillaja Saponaria Molina and not fraction A of Quillaja Saponaria Molina.

9. The method of claim 8 , wherein the two iscom matrix particles are present in a composition of about 70% (w/w) of the first iscom particle and about 30% (w/w) of the second iscom particle.

10. The method of claim 8 , wherein the two iscom matrix particles are present in a composition of about 85% (w/w) of the first iscom particle and about 15% (w/w) of the second iscom particle.

11. The method of claim 7 , wherein the adjuvant comprises iscom matrix particles comprising a mixture of fraction A of Quillaja Saponaria Molina and fraction C of Quillaja Saponaria Molina.

12. The method of claim 11 , wherein the mixture comprises about 70% (w/w) of fraction A of Quillaja Saponaria Molina and about 30% (w/w) of fraction C of Quillaja Saponaria Molina.

13. The method of claim 11 , wherein the mixture comprises about 85% (w/w) of fraction A of Quillaja Saponaria Molina and about 15% (w/w) of fraction C of Quillaja Saponaria Molina.

14. The method of claim 7 , wherein the adjuvant is an alum adjuvant.

15. The method of claim 1 , wherein the composition contains no added adjuvant.

16. The method of claim 1 , wherein a dose of the vaccine composition is administered in a volume of about 0.5 mL.

17. The method of claim 1 , wherein a dose of the vaccine composition comprises about 87.5 μg to about 162.5 μg of an RSV F glycoprotein.

18. The method of claim 1 , wherein a dose of the vaccine composition comprises about 100 μg to about 300 μg of an RSV F glycoprotein.

19. The method of claim 1 , wherein a dose of the vaccine composition comprises about 120 μg to about 130 μg of an RSV F glycoprotein.

20. The method of claim 1 , wherein the RSV F glycoprotein comprises a deletion of 1 to 10 amino acids corresponding to amino acids 137-146 of SEQ ID NO:2 and an inactivated primary furin cleavage site corresponding to amino acids 131 to 136 of SEQ ID NO: 2, wherein the primary furin cleavage site is inactivated by mutation.

21. The method of claim 20 , wherein the RSV F glycoprotein is selected from the group consisting of SEQ ID NOS:3-12 and variants of SEQ ID NOS:3-12 lacking part or all of the N-terminal signal peptide.

22. The method of claim 21 , wherein the RSV F glycoprotein comprises SEQ ID NO:19.

23. The method of claim 21 , wherein the RSV F glycoprotein consists of SEQ ID NO:19.

24. The method of claim 1 , wherein the molar ratio is about 50:1.

25. The method of claim 1 , wherein the pharmaceutically acceptable buffer comprises
(i) sodium phosphate at about 15 mM to about 25 mM;
(ii) sodium chloride at about 150 mM;
(iii) histidine at 0.25% w/v to 2% w/v;

wherein the pH of the composition is between 5.8 and 6.4.

26. The method of claim 1 , wherein the pharmaceutically acceptable buffer comprises
(i) sodium phosphate at about 22 mM;
(ii) sodium chloride at about 150 mM;
(iii) histidine at about 1% w/v;

wherein the pH of the composition is about 6.2.

27. The method of claim 1 , wherein the RSV F glycoprotein comprises an RSV F1 and an RSV F2 domain connected by a disulfide bond.

Assignees

• Novavax Inc

Inventors

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

Classifications

• 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

• A61P31/16

  for influenza or rhinoviruses · CPC title

• A61K47/183

  Amino acids, e.g. glycine, EDTA or aspartame · CPC title

• A61K39/39

  characterised by the immunostimulating additives, e.g. chemical adjuvants · CPC title

• A61K39/385 Primary

  Haptens or antigens, bound to carriers · CPC title