Zika virus vaccine

• US 10,639,365 B2
• Filed: 12/23/2016
• Issued: 05/05/2020
• Est. Priority Date: 12/23/2015
• Status: Active Grant

• Current Assignee: Valneva Austria Gmbh (Valneva SE)
• Original Assignee: Valneva Austria Gmbh (Valneva SE)
• Inventors: Barbero Calzado, Jana, Nebenfuhr, Mario, Schlegl, Robert, Weber, Michael, Heindl-Wruss, Jurgen
• Primary Examiner(s): Chestnut, Barry A
• Application Number:
  US16/063,007
• Publication Number:
  US 20180371027A1
• Time in Patent Office: 1,229 Days
• CPC Class Codes: A61K 2039/5252 inactivated (killed)
• CPC Class Codes: A61K 2039/5254 avirulent or attenuated
• CPC Class Codes: A61K 2039/5258 Virus-like particles
• CPC Class Codes: A61K 2039/55505 Inorganic adjuvants
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: A61K 39/39 characterised by the immunostimulating additives, e.g. chemical adjuvants
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: C07K 14/18 Togaviridae; Flaviviridae
• CPC Class Codes: C07K 14/1825 Flaviviruses or Group B arboviruses, e.g. yellow fever virus, japanese encephalitis, tick-borne encephalitis, dengue
• CPC Class Codes: C12N 2770/24134 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 2770/24151 Methods of production or purification of viral material
• CPC Class Codes: C12N 2770/24163 by chemical treatment
• CPC Class Codes: C12N 2770/36151 Methods of production or purification of viral material
• CPC Class Codes: C12N 7/00 Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00
• CPC Class Codes: C12N 7/02 Recovery or purification
• CPC Class Codes: C12N 7/06 Inactivation or attenuation by chemical treatment
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Described herein are Zika virus vaccines and compositions and methods of producing and administering said vaccines to subjects in need thereof.

Claims

1. A Zika virus vaccine comprising an inactivated Zika virus, wherein the Zika virus vaccine contains protamine sulphate (PS) or fragments or break-down products of PS at amounts below 1 μ

g/mL and wherein the vaccine is able to confer seroprotection on at least 70% of subjects that are administered the Zika virus vaccine.

2. The Zika virus vaccine of claim 1, wherein the Zika virus vaccine is able to confer seroprotection on at least 80%, of subjects that are administered the Zika virus vaccine.

3. The Zika virus vaccine of claim 1, wherein the Zika virus comprises an RNA genome corresponding to the DNA sequence provided by any one of the nucleic acid sequences of SEQ ID NOs:

2-13 or 72, or a variant nucleic acid sequence that is at least 88% identical to any one of SEQ ID NOs;

2-13 or 72 and able to pack a virulent Zika virus.

4. The Zika virus vaccine of claim 1, wherein the Zika virus comprises an E protein selected from the amino acid sequences provided by any one of SEQ ID NOs:

14-69, or a variant amino acid sequence that is at least 95% identical to any one of SEQ ID NOs;

14-69 and able to pack a virulent Zika virus.

5. The Zika virus vaccine of claim 1, wherein the Zika virus is inactivated by chemical inactivation, thermal inactivation, pH inactivation, or UV inactivation.

6. The Zika virus vaccine of claim 5, wherein the chemical inactivation comprises contacting the Zika virus with a chemical inactivation agent for longer than is required to completely inactivate the Zika virus as measured by plaque assay.

7. The Zika virus vaccine of claim 6, wherein the chemical inactivation comprises contacting the Zika virus with formaldehyde.

8. The Zika virus vaccine of claim 7, wherein the formaldehyde inactivation comprises contacting the Zika virus with formaldehyde for between 2-10 days.

9. The Zika virus vaccine of claim 5, wherein the chemical activation is performed at about +4°

C. or about +22°

C.

10. The Zika virus vaccine of claim 1, further comprising an adjuvant.

11. The Zika virus vaccine of claim 10, wherein the adjuvant is an aluminum salt adjuvant.

12. The Zika virus vaccine of claim 11, wherein the aluminum salt adjuvant is aluminium hydroxide or aluminium phosphate salt.

13. The Zika virus vaccine of claim 10, wherein the vaccine comprises or further comprises an adjuvant comprising a peptide and a deoxyinosine-containing immunostimulatory oligodeoxynucleic acid molecule (I-ODN).

14. The Zika virus vaccine of claim 13, wherein the peptide comprises the sequence KLKL5KLK (SEQ ID NO:

71) and the I-ODN comprises oligo-d(IC)13 (SEQ ID NO;

     70).

15. The Zika virus vaccine of claim 1, further comprising one or more pharmaceutically acceptable excipients.

16. The Zika virus vaccine of claim 1, wherein the Zika virus vaccine contains protamine sulphate (PS) or fragments or break-down products of PS at amounts below 100 ng/mL.

17. The Zika virus vaccine of claim 1, wherein said protamine sulphate (PS) or fragments or break-down products of PS can be detected by mass spectroscopy or another sensitive method.

18. The Zika virus vaccine of claim 1, wherein said Zika virus vaccine is able to confer seroprotection on at least 90% of subjects that are administered the Zika virus vaccine.

19. The Zika virus vaccine of claim 1, wherein said Zika virus vaccine is able to confer seroprotection on at least 95% of subjects that are administered the Zika virus vaccine.

20. The Zika virus vaccine of claim 11, wherein said aluminium salt adjuvant is aluminium hydroxide with less than 1.25 parts per billion (ppb) copper (Cu) based on the final pharmaceutical composition comprising the Zika virus.