Recombinant respiratory syncytial virus g protein fragments

Patent metadata

Field	Value
Publication number	US-2016304565-A1
Application number	US-201415100914-A
Country	US
Kind code	A1
Filing date	Dec 2, 2014
Priority date	Dec 2, 2013
Publication date	Oct 20, 2016
Grant date	—

Abstract

Compositions and methods useful for producing an immune response in a subject specific for the RSV G protein are described herein. The new methods and compositions described herein are made possible by the development of a new recombinant RSV G protein fragment, which has been engineered) for in vitro production and is antigenically similar to the native RSV G protein. The recombinant RSV G protein fragment is capable of inducing the production of RSV G-specific antibodies when injected into a subject. These antibodies can recognize both RSV A and RSV B strains and inhibit infection of both viruses. Accordingly, the compositions and methods described herein may be useful in protecting subjects from RSV infection via immunization, raising antibodies specific for RSV, which can in turn be used to treat RSV infection.

First claim

What is claimed:

1 . A recombinant polypeptide comprising a fragment of an RSV G amino acid sequence.

2 . The recombinant polypeptide of claim 1 , wherein the fragment of the RSV G protein does not include a transmembrane domain.

3 . The recombinant polypeptide of claim 1 or 2 , wherein the fragment of the RSV G protein is composed of a subsection of the ectodomain of an RSV G protein.

4 . The recombinant polypeptide of any one of the previous claims, comprising amino acid residues 67-298 of a G protein from an RSV.

5 . The recombinant polypeptide of any one of the previous claims, wherein said recombinant polypeptide comprises the sequence of SEQ ID NO: 2.

6 . The recombinant polypeptide of any one of the previous claims, wherein said recombinant polypeptide further comprises an epitope tag.

7 . The recombinant polypeptide of claim 6 , wherein said epitope tag is a polyhistidine tag.

8 . The recombinant polypeptide of claim 6 or 7 , wherein said polypeptide further comprises an enzyme cleavage site between the RSV G peptide segment and the epitope tag.

9 . A recombinant polynucleotide comprising a sequence that encodes the recombinant polypeptide of any one of the previous claims.

10 . The recombinant polynucleotide of claim 9 , wherein said polynucleotide is codon optimized for expression in a: mammalian cell, insect cell, yeast, or bacterium.

11 . The recombinant polynucleotide of claim 9 or 10 , wherein said polynucleotide is codon optimized for expression in E. coli.

12 . The recombinant polynucleotide of any one of claims 9 - 11 , wherein said polynucleotide comprises the sequence of SEQ ID NO: 1.

13 . The recombinant polynucleotide of claim 12 , wherein said polynucleotide consists of the sequence of SEQ ID NO: 1 and a sequence encoding a cleavage site and en epitope tag.

14 . The recombinant polynucleotide of claim 12 , wherein said polynucleotide consists of the sequence of SEQ ID NO: 1.

15 . A vector comprising the recombinant polynucleotide of any one of claims 9 - 14 .

16 . The vector of claim 15 , wherein said vector is a viral vector or a non-viral expression vector.

17 . The vector of claim 16 , wherein said non-viral expression vector is the pSK vector.

18 . A recombinant cell comprising the recombinant polynucleotide of any one of claims 9 - 14 .

19 . A recombinant cell comprising the vector of any one of claims 15 - 17 .

20 . The cell of claim 18 or 19 , wherein said cell is a mammalian cell, insect cell, yeast, or bacterium.

21 . The cell of claim 20 , wherein said cell is an E. coli.

22 . A method of generating an immune response in a subject, comprising administering to the subject any one of the recombinant poly peptide of any one of claims 1 - 8 .

23 . The method of claim 22 , wherein said recombinant polypeptide is administered in an amount sufficient to elicit an immune response by the subject.

24 . The method of claim 23 , wherein said amount is any one of: 0.1 μg/kg to 100 μg/kg.

25 . The method of any one of claims 22 - 24 , wherein said recombinant poly peptide is also administered with an adjuvant.

26 . A method of generating an immune response in a subject, comprising administering to the subject any one of the recombinant polynucleotides of any one of claims 9 - 14 .

27 . The method of claim 26 , wherein said recombinant polypeptide is administered in an amount sufficient to elicit an immune response by the subject.

28 . The method of claim 26 or 27 , wherein said recombinant polypeptide is also administered with an adjuvant.

29 . An isolated antibody produced by the method of any one of claims 22 - 28 .

30 . A pharmaceutical composition comprising the recombinant polypeptide of any one of claims 1 - 8 .

31 . A pharmaceutical composition comprising the recombinant polynucleotides of any one of claims 9 - 14 .

32 . A oligomeric compound, comprising at least two of the recombinant polypeptides of any one of the claims 1 - 8 .

Assignees

• Us Health

Inventors

• Khurana Surender
• Golding Hana

Classifications

• C07K16/11

  Paramyxoviridae (F); Pneumoviridae (F), e.g. respiratory syncytial virus [RSV] · CPC title

• C12N2760/18522

  New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes · CPC title

• A61K2039/53

  DNA (RNA) vaccination · CPC title

• A61K2039/525

  Virus · CPC title

• A61K39/155 Primary

  Paramyxoviridae, e.g. parainfluenza virus · CPC title