Nucleic acid lipid particle vaccines

Abstract

Provided herein are vaccines for preventing and / or treating infection caused by novel coronavirus (severe acute respiratory syndrome coronavirus 2: SARS-CoV-2). Lipid particles encapsulating a nucleic acid capable of expressing S protein and / or a fragment thereof of novel coronavirus (severe acute respiratory syndrome coronavirus 2: SARS-CoV-2), wherein the lipid comprises a cationic lipid represented by general formula (Ia), or a pharmaceutically acceptable salt thereof. In the formula, R 1 and R 2 independently represent C1-C3 alkyl; L 1 represents C 17 -C 19 alkylene optionally having 1 or more C2-C4 alkanoyloxy groups; L 2 represents C 10 -C 19 alkyl, or C 10 -C 19 alkylene optionally having 1 or more C2-C4 alkanoyloxy groups; p is 3 or 4.

Claims

1. Lipid particles, which encapsulate nucleic acid fragments capable of expressing the S protein of SARS-CoV-2, wherein, The S protein fragment consists of the S protein signaling sequence and the receptor-binding domain. Lipid particles include cationic lipids, amphiphilic lipids, sterols, and PEG lipids. Cationic lipids are composed of the following structural formula: The indicated cationic lipids, or their pharmaceutically permissible salts, The amphiphilic lipid is distearate phosphatidylcholine (DSPC). Sterols are cholesterol. The PEG lipid is 1,2-dimyristic-sn-glycerol methoxy polyethylene glycol.

2. The lipid particles of claim 1, wherein, The lipid composition of amphiphilic lipids, sterols, cationic lipids, and PEG lipids is in molar weight, with amphiphilic lipids accounting for less than 15%, sterols for 20-55%, cationic lipids for 40-65%, and PEG lipids for 1-5%, and the ratio of total lipid weight to nucleic acid weight is 15-30.

3. The lipid particles of claim 2, wherein, The lipid composition of amphiphilic lipids, sterols, cationic lipids, and PEG lipids is in molar weight, with amphiphilic lipids accounting for 10-15%, sterols for 35-45%, cationic lipids for 40-50%, and PEG lipids for 1-2%, and the ratio of total lipid weight to nucleic acid weight is 17.5-22.

5.

4. The lipid particles according to any one of claims 1 to 3, wherein, The nucleic acid that can express the S protein fragment of SARS-CoV-2 is an mRNA containing a cap structure, a 5' untranslated region (5'-UTR), a leader sequence, the translated region of the receptor-binding domain of the S protein, a 3' untranslated region (3'-UTR), and a polyA tail.

5. The lipid particles of claim 4, wherein, The 5' untranslated region (5'-UTR) and the 3' untranslated region (3'-UTR) are the 5'-UTR sequence and the 3'-UTR sequence of human β-globin, respectively.

6. The lipid particles according to any one of claims 1 to 3, wherein, Nucleic acids contain at least one modified nucleotide.

7. The lipid particles of claim 6, wherein, The modified nucleotide is selected from at least one of 5-methylcytidine, 5-methoxyuridine, 5-methyluridine, pseudouridine, and 1-alkylpseudouridine.

8. The lipid particles according to any one of claims 1 to 3, wherein, The average particle size of lipid particles is 30 nm to 300 nm.

9. The lipid particles of claim 1, wherein, The amino acid sequence of the receptor-binding domain of the S protein is selected from the amino acid sequence numbered 94 to 107.

10. The use of the lipid particles according to any one of claims 1 to 9 in the preparation of compositions for the prevention and / or treatment of infection caused by SARS-CoV-2.

11. A composition comprising the lipid particles described in any one of claims 1 to 9.

12. The composition of claim 11, further comprising a buffer solution containing sucrose and histidine.

13. The composition of claim 11 or 12, wherein it is a pharmaceutical composition.

14. Use of the lipid particles according to any one of claims 1 to 9 in the preparation of a SARS-CoV-2 vaccine.

15. A method for preparing lipid particles according to any one of claims 1 to 9, comprising the step of obtaining a dispersion of nucleic acid lipid particles by mixing an ethanol solution and a buffer solution in a flow path, wherein the ethanol solution comprises cationic lipids, amphiphilic lipids, sterols and PEG lipids, and the buffer solution comprises nucleic acids capable of expressing fragments of the S protein of SARS-CoV-2.

16. The preparation method of claim 15, further comprising the step of dialyzing the dispersion of the nucleic acid lipid particles with a buffer containing sucrose and histidine.

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