Zika virus purification
Described herein are improved purification methods for Zika virus vaccines and compositions. Also described are Zika vaccines and methods of producing and administering said Zika vaccines to subjects in need thereof.
1. A Zika virus vaccine comprising Zika virus particles grown on Vero cells and subsequently inactivated, and further comprising minor amounts of protamine sulphate and/or fragments thereof, wherein said minor amounts are below the detection limit when measured with high performance liquid chromatography (HPLC) but are still detectable by mass spectroscopy, and wherein said Zika virus particles grown on Vero cells are purified by protamine sulphate precipitation and sucrose gradient centrifugation, wherein said sucrose gradient centrifugation comprises a Zika virus comprising fraction in a 10% (w/w) sucrose solution and three further layers of sucrose solutions comprising a first sucrose solution comprising about 15% (w/w) sucrose, a second sucrose solution comprising about 35% (w/w) sucrose, and a third sucrose solution comprising about 50% (w/w) sucrose.
2. The Zika virus vaccine of claim 1 , wherein said Zika virus vaccine is able to confer seroprotection on at least 70% of subjects that are administered said Zika virus vaccine.
3. The Zika virus vaccine of claim 1 , wherein said Zika virus particles have an RNA genome corresponding to the DNA sequence provided by any one of the nucleic acid sequences of SEQ ID NOs: 2-13, or a variant nucleic acid sequence that is at least 88% identical to any one of SEQ ID NOs: 2-13 and able to pack a virulent Zika virus when grown in host cells.
4. The Zika virus vaccine of claim 1 , wherein said Zika virus particles have an E protein selected from the amino acid sequences of 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 when grown in host cells.
5. The Zika virus vaccine of claim 1 , further comprising an adjuvant.
6. The Zika virus vaccine of claim 5 , wherein said adjuvant is an aluminium salt adjuvant.
7. The Zika virus vaccine of claim 6 , wherein said aluminium salt adjuvant is aluminium hydroxide or aluminium phosphate.
8. The Zika virus vaccine of claim 6 , wherein said aluminum salt adjuvant is aluminium hydroxide with less than 1.25 ppb Cu based on the final composition comprising said Zika virus.
9. The Zika virus vaccine of claim 1 , further comprising one or more pharmaceutically acceptable excipient(s).