Attenuated reovirus-based vaccine composition and its uses

Abstract

The present invention relates to an attenuated reovirus-based vaccine composition and its use. The attenuated reovirus according to the present invention is obtained by truncating the 251st to 455th amino acids from the sigma 1 protein of the capsid. When an epitope of an antigenic protein that induces cancer or an infectious disease is introduced into the truncated sigma 1 protein site, the epitope of the antigenic protein is stably expressed in cells and has the effect of producing neutralizing antibodies or eliciting immune responses such as inducing cellular immunity. Thus, by introducing an epitope of an antigenic protein into the truncated sigma 1 protein site of the attenuated reovirus according to the present invention, it is expected that the composition can be usefully used as a vaccine composition against cancer or infectious diseases.

Claims

1. (i) the amino acid sequence of a weakened reovirus sigma-1 protein, where the weakened reovirus sigma-1 protein consists of the amino acid sequences of positions 1 to 250 of a wild-type reovirus sigma-1 protein with the 251st amino acid from the N-terminus cleaved, and the weakened reovirus sigma-1 protein is represented by the amino acid sequence of Sequence ID No. 1; and (ii) an epitope amino acid sequence of an antigen that induces cancer or infectious disease, wherein the epitope amino acid sequence is inserted into the amino acid sequence of the attenuated reovirus sigma-1 protein, including the 251st amino acid from the N-terminus and thereafter. A polypeptide consisting of the following:

2. The polypeptide according to claim 1, characterized in that the epitope forms a fusion protein at the carboxyl terminus of a weakened reovirus sigma 1 protein.

3. The polypeptide according to claim 1, characterized in that the cancer is at least one selected from the group consisting of liver cancer, glioma, sarcoma, colorectal cancer, breast cancer, prostate cancer, melanoma, lung cancer, head and neck cancer, ovarian cancer, bladder cancer, stomach cancer, esophageal cancer, bile duct cancer, pancreatic cancer, cervical cancer, skin cancer, lymphoma, thyroid cancer, bone marrow cancer, endometrial cancer, kidney cancer, rectal cancer, and brain tumor.

4. The polypeptide according to claim 1, characterized in that the infectious disease is at least one selected from the group consisting of coronavirus infection-19 (COVID-19), hepatitis C, influenza, human immunodeficiency virus (HIV)-induced AIDS (AIDS), tuberculosis, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), infant enteritis caused by rotavirus, and nonbacterial acute gastroenteritis caused by norovirus.

5. The polypeptide according to claim 1, characterized in that the amino acid sequence of the epitope is at least one selected from the group consisting of the amino acid sequences of SEQ ID NOs: 3 to 10.

6. The polypeptide according to claim 1, characterized in that the epitope generates neutralizing antibodies in the host or induces cellular immunity to trigger an immune response.

7. The polypeptide according to claim 1, characterized in that the epitope is at least one selected from the group consisting of CD4+ T cell, CD8+ T cell, and B cell epitopes.

8. A viral vector comprising a polynucleotide encoding a polypeptide according to any one of claims 1 to 7.

9. The viral vector according to claim 8, characterized in that the attenuated reovirus sigma-1 protein is encrypted by the base sequence represented by Sequence ID No.

2.

10. The viral vector according to claim 8, wherein the vector further comprises a polynucleotide encoding at least one selected from the group consisting of a linker, a Myc protein, a FLAG protein, and a 2A peptide, before and after the base sequence encoding the epitope, wherein the linker consists of the amino acid sequence of SEQ ID NO: 11, the Myc protein consists of the amino acid sequence of SEQ ID NO: 12, and the FLAG protein consists of the amino acid sequence of SEQ ID NO:

13.

11. The viral vector according to claim 8, characterized in that the base sequence encoding the epitope is substituted or inserted at base positions 763 to 1416 from the 5' end of the base sequence encoding the attenuated reovirus sigma 1 protein.

12. A vaccine composition comprising a polypeptide according to any one of claims 1 to 7, a polynucleotide encoding the same, or a viral vector according to claim 8 as an active ingredient.

13. The vaccine composition according to claim 12, characterized in that the vaccine composition is for the prevention or treatment of cancer or infectious disease.

14. A method for producing a vaccine composition, including the following steps: a) A step of producing a deevolutionary viral vector containing a nucleotide sequence encoding a weakened reovirus sigma-1 protein, wherein the weakened reovirus sigma-1 protein consists of the amino acid sequences from positions 1 to 250 of the wild-type reovirus sigma-1 protein with the 251st amino acid from the N-terminus cleaved, and is represented by the amino acid sequence of Sequence ID No. 1, and b) A step in which a polynucleotide is introduced into the vector, in which a nucleotide sequence encoding an epitope of an antigen that induces cancer or infectious disease is inserted or substituted at positions 763 to 1416 from the 5' end of the nucleotide sequence encoding the attenuated reovirus sigma 1 protein, thereby expressing the attenuated reovirus sigma 1 protein fused with the epitope of the antigen that induces cancer or infectious disease.

15. c) A method for producing a vaccine composition according to claim 14, further comprising the step of producing and proliferating a vector containing the polynucleotide from step b) in at least one cell selected from the group consisting of BHK21, L929, HEK293, CHO, PER. C6, HeLa, and Vero cells.

16. Use of the polypeptide according to claim 1, a polynucleotide encoding the same, or a viral vector containing the polynucleotide for the manufacture of a vaccine for the prevention or treatment of cancer or infectious disease.

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