Truncated Rotavirus VP4 Protein And Application Thereof

Patent metadata

Field	Value
Publication number	US-2018141978-A1
Application number	US-201615575140-A
Country	US
Kind code	A1
Filing date	May 20, 2016
Priority date	May 21, 2015
Publication date	May 24, 2018
Grant date	—

Abstract

The invention relates to a truncated rotavirus VP4 protein, a sequence encoding the same, a method for preparing the same, and a pharmaceutical composition and a vaccine comprising the protein, wherein the protein, the pharmaceutical composition and the vaccine are useful for preventing, alleviating or treating rotavirus infection and a disease caused by rotavirus infection, such as rotavirus gastroenteritis and diarrhea. The invention further relates to use of the protein in the manufacture of a pharmaceutical composition or a vaccine for preventing, alleviating or treating rotavirus infection and a disease caused by rotavirus infection, such as rotavirus gastroenteritis and diarrhea.

First claim

1 . A truncated rotavirus VP4 protein or a variant thereof, wherein as compared to a wild-type rotavirus VP4 protein, the truncated rotavirus VP4 protein has 1-64 amino acids (e.g., 5-64 amino acids) truncated at N-terminal, and has C-terminal ended at the following position of the wild-type rotavirus VP4 protein: a position corresponding to any position among the amino acid positions 276-497 of SEQ ID NO: 40.

2 . An isolated nucleic acid, encoding the truncated rotavirus VP4 protein or variant thereof according to claim 1 .

3 . A vector comprising the isolated nucleic acid according to claim 2 .

4 . A host cell comprising the isolated nucleic acid according to claim 2 or a vector comprising the isolated nucleic acid.

5 . A polymer comprising or consisting of the truncated rotavirus VP4 protein or variant thereof according to claim 1 .

6 . A composition comprising anyone of the following:
(1) the truncated rotavirus VP4 protein or variant thereof according to claim 1 , or ( 2 ) an isolated nucleic acid encoding the truncated rotavirus VP4 protein or variant thereof of (1), or (3) a vector comprising the isolated nucleic acid of (2), or (4) a host cell comprising the isolated nucleic acid of (2), or (5) a polymer comprising or consisting of the truncated rotavirus VP4 protein or variant thereof of (1).

7 . A pharmaceutical composition, comprising (1) the truncated rotavirus VP4 protein or variant thereof according to claim 1 or a polymer comprising or consisting of the truncated rotavirus VP4 protein or variant thereof, and (2) optionally, a pharmaceutically acceptable carrier and/or excipient.

8 . A method for preparing the truncated rotavirus VP4 protein or variant thereof according to claim 1 , comprising, under a condition that allows expression of the truncated protein or variant thereof, culturing a host cell comprising an isolated nucleic acid encoding the truncated rotavirus VP4 protein or variant thereof; and, recovering the expressed truncated protein or variant thereof.

9 . A method for preparing a vaccine, comprising mixing the truncated rotavirus VP4 protein or variant thereof according to claim 1 or a polymer comprising or consisting of the truncated rotavirus VP4 protein or variant thereof with a pharmaceutically acceptable carrier and/or excipient, and optionally, with an adjuvant and/or an additional active ingredient.

10 . A method for preventing or treating rotavirus infection or a disease caused by rotavirus infection, comprising administering to a subject a prophylactically or therapeutically effective amount of the truncated rotavirus VP4 protein or variant thereof according to claim 1 , or a polymer comprising or consisting of the truncated rotavirus VP4 protein or variant thereof, or a pharmaceutical composition comprising the truncated rotavirus VP4 protein or variant thereof or the polymer.

11 . (canceled)

12 . (canceled)

13 . The truncated rotavirus VP4 protein or variant thereof according to claim 1 , wherein as compared to the wild-type rotavirus VP4 protein, the truncated rotavirus VP4 protein has 1-5, 5-21, 21-25 or 25-64 amino acids truncated at N-terminal; and has C-terminal ended at the following position of the wild-type rotavirus VP4 protein: a position corresponding to any position among the amino acid positions 276-497, 281-497, 291-497, 301-497, 311-497, 321-497, 331-497, 341-497, 351-497, 361-497, 371-497, 381-497, 391-497, 401-497, 411-497, 421-497, 431-497, 441-497, 451-497, 461-497, 471-497, 476-497, 482-497, 487-497, or 492-497 of SEQ ID NO: 40.

14 . The truncated rotavirus VP4 protein or variant thereof according to claim 1 , wherein as compared to the wild-type rotavirus VP4 protein, the truncated rotavirus VP4 protein has 1, 5, 21, 25 or 64 amino acids truncated at N-terminal, and has C-terminal ended at the following position of the wild-type rotavirus VP4 protein: a position corresponding to the amino acid position 281, 291, 301, 311, 321, 331, 341, 351, 361, 371, 381, 391, 401, 411, 421, 431, 441, 451, 461, 471, 476, 482, 487, 492 or 497 of SEQ ID NO: 40.

15 . The truncated rotavirus VP4 protein or variant thereof according to claim 1 , wherein as compared to the wild-type rotavirus VP4 protein, the truncated rotavirus VP4 protein has 25 amino acids truncated at N-terminal and has C-terminal ended at the following position: a position corresponding to the amino acid position 331, 351, 381, 411, 441, 461, 471, 476, 482, 487, 492 or 497 of SEQ ID NO: 40; or, the truncated rotavirus VP4 protein has 1, 5, 21, 25 or 64 amino acids truncated at N-terminal and has C-terminal ended at the following position: a position corresponding to the amino acid position 476 of SEQ ID NO: 40.

16 . The truncated rotavirus VP4 protein or variant thereof according to claim 1 , wherein the wild-type rotavirus VP4 protein is a VP4 protein derived from rotavirus LLR strain, SAl 1 strain, or EDIM strain, or a VP4 protein derived from a rotavirus of P[4], P[6], or P[8] genotype.

17 . The truncated rotavirus VP4 protein or variant thereof according to claim 1 , wherein the wild-type rotavirus VP4 protein has an amino acid sequence selected from: SEQ ID NO: 40 and 87-91.

18 . The truncated rotavirus VP4 protein or variant thereof according to claim 1 , wherein the truncated rotavirus VP4 protein has an amino acid sequence selected from: SEQ ID NO: 2-5 and 10-39.

19 . The pharmaceutical composition according to claim 7 , wherein the pharmaceutical composition is characterized by one or more of the following items:
(1) the pharmaceutical composition further comprises an adjuvant; (2) the truncated protein or variant thereof or the polymer is present in an amount effective for preventing or treating rotavirus infection or a disease caused by rotavirus infection; (3) the pharmaceutical composition further comprises an additional active ingredient; and (4) the pharmaceutical composition is a vaccine.

20 . The pharmaceutical composition according to claim 19 , wherein the adjuvant is aluminum adjuvant.

21 . The method according to claim 10 , wherein the disease caused by rotavirus infection is rotavirus gastroenteritis or diarrhea.

22 . The method according to claim 10 , wherein the subject is a mammal.

23 . The method according to claim 10 , wherein the subject is mouse or human.

Assignees

• Univ Xiamen

Inventors

• Ge Shengxiang
• Li Tingdong
• Jia Lianzhi
• Li Yijian
• Xue Miaoge
• Zeng Yuanjun
• Zhang Jun
• Xia Ningshao

Classifications

• A61P31/14

  for RNA viruses · CPC title

• A61P1/00

  Drugs for disorders of the alimentary tract or the digestive system · CPC title

• A61K2039/552

  Veterinary vaccine · CPC title

• A61P1/12

  Antidiarrhoeals · CPC title

• A61K39/15

  Reoviridae, e.g. calf diarrhea virus · CPC title