Vaccine compositions having improved stability and immunogenicity

Patent metadata

Field	Value
Publication number	US-2020101151-A1
Application number	US-201916545424-A
Country	US
Kind code	A1
Filing date	Aug 20, 2019
Priority date	Sep 3, 2015
Publication date	Apr 2, 2020
Grant date	—

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

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

• C12N2760/14134

  Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein · CPC title

• 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

• C12N2760/18534

  Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein · CPC title

• C12N2760/16251

  Methods of production or purification of viral material · CPC title

• A61K2039/54

  characterised by the route of administration · CPC title