Egg allergy antigen

Abstract

The present invention provides a novel antigen for an egg allergy, a method for diagnosing an egg allergy and a kit for diagnosing an egg allergy, a pharmaceutical composition comprising the antigen, an egg, a processed product of an egg, or a bird which lays or has hatched from the egg in which the antigen is eliminated or reduced, a method for producing a processed product of an egg in which the antigen is eliminated or reduced, and a tester for determining the presence or absence of an egg antigen in an object of interest.

1 . A kit for diagnosing an egg allergy, the kit comprising, as an antigen, at least one protein defined in any one of the following (1) to (3):
 (1) (1A) a protein comprising a C-terminal portion of Vitellogenin-3 or a variant thereof, which is defined below in any of (1A-a) to (1A-e) which is an antigen for the egg allergy:
 (1A-a) a protein comprising an amino acid sequence with deletion, substitution, insertion or addition of one or several amino acids in SEQ ID NO: 2; 
 (1A-b) a protein comprising an amino acid sequence having at least 70% identity to the amino acid sequence of SEQ ID NO: 2; 
 (1A-c) a protein comprising an amino acid sequence encoded by a nucleotide sequence with deletion, substitution, insertion or addition of one or several nucleotides in SEQ ID NO: 1; 
 (1A-d) a protein comprising an amino acid sequence encoded by a nucleotide sequence having at least 70% identity to the nucleotide sequence of SEQ ID NO: 1; or 
 (1A-e) a protein comprising an amino acid sequence encoded by a nucleic acid that hybridizes under stringent conditions with a nucleic acid having a nucleotide sequence complementary to the nucleotide sequence of SEQ ID NO: 1; or 
 (1B) a protein comprising at least one amino acid sequence selected from the group consisting of SEQ ID NOs: 2-11; 
   (2) (2A) a protein comprising a C-terminal portion of Vitellogenin-3 or a variant thereof, which is defined below in any of (2A-a) to (2A-e) which is an antigen for the egg allergy:
 (2A-a) a protein comprising an amino acid sequence with deletion, substitution, insertion or addition of one or several amino acids in SEQ ID NO: 13; 
 (2A-b) a protein comprising an amino acid sequence having at least 70% identity to the amino acid sequence of SEQ ID NO: 13; 
 (2A-c) a protein comprising an amino acid sequence encoded by a nucleotide sequence with deletion, substitution, insertion or addition of one or several nucleotides in SEQ ID NO: 12; 
 (2A-d) a protein comprising an amino acid sequence encoded by a nucleotide sequence having at least 70% identity to the nucleotide sequence of SEQ ID NO: 12; or 
 (2A-e) a protein comprising an amino acid sequence encoded by a nucleic acid that hybridizes under stringent conditions with a nucleic acid having a nucleotide sequence complementary to the nucleotide sequence of SEQ ID NO: 12; or 
 (2B) a protein comprising at least one amino acid sequence selected from the group consisting of SEQ ID NOs: 9-11, 13, 14, and 16; 
   (3) (3A) A protein comprising a middle portion of Vitellogenin-1 or a C-terminal portion of Lipovitelin-1 or a variant thereof, which is defined below in any of (3A-a) to (3A-e) which is an antigen for the egg allergy:
 (3A-a) a protein comprising an amino acid sequence with deletion, substitution, insertion or addition of one or several amino acids in SEQ ID NO: 18; 
 (3A-b) a protein comprising an amino acid sequence having at least 70% identity to the amino acid sequence of SEQ ID NO: 18; 
 (3A-c) a protein comprising an amino acid sequence encoded by a nucleotide sequence with deletion, substitution, insertion or addition of one or several nucleotides in SEQ ID NO: 17; 
 (3A-d) a protein comprising an amino acid sequence encoded by a nucleotide sequence having at least 70% identity to the nucleotide sequence of SEQ ID NO: 17; or 
 (3A-e) a protein comprising an amino acid sequence encoded by a nucleic acid that hybridizes under stringent conditions with a nucleic acid having a nucleotide sequence complementary to the nucleotide sequence of SEQ ID NO: 17; or 
 (3B) a protein comprising at least one amino acid sequence selected from the group consisting of SEQ ID NOs: 18-45. 
   
     
     
         2 . A kit for diagnosing an egg allergy, the kit comprising, as an antigen, at least one protein defined in any one of the following (4) to (10):
 (4) (4A) a protein comprising Vitellogenin-3 or a variant thereof, which is defined below in any of (4A-a) to (4A-e) which is an antigen for the egg allergy:
 (4A-a) a protein comprising an amino acid sequence with deletion, substitution, insertion or addition of one or several amino acids in SEQ ID NO: 47; 
 (4A-b) a protein comprising an amino acid sequence having at least 70% identity to the amino acid sequence of SEQ ID NO: 47; 
 (4A-c) a protein comprising an amino acid sequence encoded by a nucleotide sequence with deletion, substitution, insertion or addition of one or several nucleotides in SEQ ID NO: 46; 
 (4A-d) a protein comprising an amino acid sequence encoded by a nucleotide sequence having at least 70% identity to the nucleotide sequence of SEQ ID NO: 46; or 
 (4A-e) a protein comprising an amino acid sequence encoded by a nucleic acid that hybridizes under stringent conditions with a nucleic acid having a nucleotide sequence complementary to the nucleotide sequence of SEQ ID NO: 46; or 
 (4B) a protein comprising at least one amino acid sequence selected from the group consisting of SEQ ID NOs: 47-57, 
   (5) (5A) a protein comprising a Vitellogenin-2 precursor or a variant thereof, which is defined below in any of (5A-a) to (5A-e) which is an antigen for the egg allergy:
 (5A-a) a protein comprising an amino acid sequence with deletion, substitution, insertion or addition of one or several amino acids in SEQ ID NO: 59; 
 (5A-b) a protein comprising an amino acid sequence having at least 70% identity to the amino acid sequence of SEQ ID NO: 59; 
 (5A-c) a protein comprising an amino acid sequence encoded by a nucleotide sequence with deletion, substitution, insertion or addition of one or several nucleotides in SEQ ID NO: 58; 
 (5A-d) a protein comprising an amino acid sequence encoded by a nucleotide sequence having at least 70% identity to the nucleotide sequence of SEQ ID NO: 58; or 
 (5A-e) a protein comprising an amino acid sequence encoded by a nucleic acid that hybridizes under stringent conditions with a nucleic acid having a nucleotide sequence complementary to the nucleotide sequence of SEQ ID NO: 58; or 
 (5B) a protein comprising at least one amino acid sequence selected from the group consisting of SEQ ID NOs: 59-104; 
   (6) (6A) a Vitellogenin-2 precursor or a variant thereof, which is defined below in any of (6A-a) to (6A-e) which is an antigen for the egg allergy:
 (6A-a) a protein comprising an amino acid sequence with deletion, substitution, insertion or addition of one or several amino acids in SEQ ID NO: 106; 
 (6A-b) a protein comprising an amino acid sequence having at least 70% identity to the amino acid sequence of SEQ ID NO: 106; 
 (6A-c) a protein comprising an amino acid sequence encoded by a nucleotide sequence with deletion, substitution, insertion or addition of one or several nucleotides in SEQ ID NO: 105; 
 (6A-d) a protein comprising an amino acid sequence encoded by a nucleotide sequence having at least 70% identity to the nucleotide sequence of SEQ ID NO: 105; or 
 (6A-e) a protein comprising an amino acid sequence encoded by a nucleic acid that hybridizes under stringent conditions with a nucleic acid having a nucleotide sequence complementary to the nucleotide sequence of SEQ ID NO: 105; or 
 (6B) a protein comprising at least one amino acid sequence selected from the group consisting of SEQ ID NOs: 106-150; 
   (7) (7A) an Apolipoprotein B precursor or a variant thereof, which is defined below in any of (7A-a) to (7A-e) which is an antigen for the egg allergy:
 (7A-a) a protein comprising an amino acid sequence with deletion, substitution, insertion or addition of one or several amino acids in SEQ ID NO: 152; 
 (7A-b) a protein comprising an amino acid sequence having at least 70% identity to the amino acid sequence of SEQ ID NO: 152; 
 (7A-c) a protein comprising an amino acid sequence encoded by a nucleotide sequence with deletion, substitution, insertion or addition of one or several nucleotides in SEQ ID NO: 151; 
 (7A-d) a protein comprising an amino acid sequence encoded by a nucleotide sequence having at least 70% identity to the nucleotide sequence of SEQ ID NO: 151; or 
 (7A-e) a protein comprising an amino acid sequence encoded by a nucleic acid that hybridizes under stringent conditions with a nucleic acid having a nucleotide sequence complementary to the nucleotide sequence of SEQ ID NO: 151; or 
 (7B) a protein comprising at least one amino acid sequence selected from the group consisting of SEQ ID NOs: 152-235; 
   (8) (8A) an Apolipoprotein B precursor or a variant thereof, which is defined below in any of (8A-a) to (8A-e) which is an antigen for the egg allergy:
 (8A-a) a protein comprising an amino acid sequence with deletion, substitution, insertion or addition of one or several amino acids in SEQ ID NO: 237; 
 (8A-b) a protein comprising an amino acid sequence having at least 70% identity to the amino acid sequence of SEQ ID NO: 237; 
 (8A-c) a protein comprising an amino acid sequence encoded by a nucleotide sequence with deletion, substitution, insertion or addition of one or several nucleotides in SEQ ID NO: 236; 
 (8A-d) a protein comprising an amino acid sequence encoded by a nucleotide sequence having at least 70% identity to the nucleotide sequence of SEQ ID NO: 236; or 
 (8A-e) a protein comprising an amino acid sequence encoded by a nucleic acid that hybridizes under stringent conditions with a nucleic acid having a nucleotide sequence complementary to the nucleotide sequence of SEQ ID NO: 236; or 
 (8B) a protein comprising at least one amino acid sequence selected from the group consisting of SEQ ID NOs: 237-249; 
   (9) (9A) an Apolipoprotein B precursor or a variant thereof, which is defined below in any of (9A-a) to (9A-e) which is an antigen for the egg allergy:
 (9A-a) a protein comprising an amino acid sequence with deletion, substitution, insertion or addition of one or several amino acids in SEQ ID NO: 251; 
 (9A-b) a protein comprising an amino acid sequence having at least 70% identity to the amino acid sequence of SEQ ID NO: 251; 
 (9A-c) a protein comprising an amino acid sequence encoded by a nucleotide sequence with deletion, substitution, insertion or addition of one or several nucleotides in SEQ ID NO: 250; 
 (9A-d) a protein comprising an amino acid sequence encoded by a nucleotide sequence having at least 70% identity to the nucleotide sequence of SEQ ID NO: 250; or 
 (9A-e) a protein comprising an amino acid sequence encoded by a nucleic acid that hybridizes under stringent conditions with a nucleic acid having a nucleotide sequence complementary to the nucleotide sequence of SEQ ID NO: 250; or 
 (9B) a protein comprising at least one amino acid sequence selected from the group consisting of SEQ ID NOs: 251-260; 
   (10) (10A) a Vitellogenin-2 precursor or a variant thereof, which is defined below in any of (10A-a) to (10A-e) which is an antigen for the egg allergy:
 (10A-a) a protein comprising an amino acid sequence with deletion, substitution, insertion or addition of one or several amino acids in SEQ ID NO: 262; 
 (10A-b) a protein comprising an amino acid sequence having at least 70% identity to the amino acid sequence of SEQ ID NO: 262; 
 (10A-c) a protein comprising an amino acid sequence encoded by a nucleotide sequence with deletion, substitution, insertion or addition of one or several nucleotides in SEQ ID NO: 261; 
 (10A-d) a protein comprising an amino acid sequence encoded by a nucleotide sequence having at least 70% identity to the nucleotide sequence of SEQ ID NO: 261; or 
 (10A-e) a protein comprising an amino acid sequence encoded by a nucleic acid that hybridizes under stringent conditions with a nucleic acid having a nucleotide sequence complementary to the nucleotide sequence of SEQ ID NO: 261; or 
 (10B) a protein comprising at least one amino acid sequence selected from the group consisting of SEQ ID NOs: 262-271. 
   
     
     
         3 . A composition for diagnosing an egg allergy, the composition comprising, as an antigen, at least one of proteins as defined in any of (1) to (3) of  claim 1 . 
     
     
         4 . A method for providing an indicator for diagnosing an egg allergy in a subject, the method comprising the steps of:
 (i) contacting a sample obtained from the subject with an antigen, wherein the sample is a solution comprising an IgE antibody;   (ii) detecting binding between an IgE antibody present in the sample from the subject and the antigen; and   (iii) when the binding between the IgE antibody in the subject and the antigen is detected, an indicator of the fact that the subject is allergic to an egg is provided;   
       wherein the antigen is at least one of proteins as defined in any of (1) to (3) of  claim 1 . 
     
     
         5 . A pharmaceutical composition comprising at least one of the proteins as defined in (1) to (3) of  claim 1 . 
     
     
         6 . The pharmaceutical composition according to  claim 5 , wherein the pharmaceutical composition is intended for the treatment of an egg allergy. 
     
     
         7 . An egg, a processed product of an egg, or a bird which lays or has hatched from the egg in which an antigen is eliminated or reduced, wherein the antigen is at least one of the proteins as defined in (1) to (3) of  claim 1 . 
     
     
         8 . A tester for determining the presence or absence of an egg antigen in an object of interest, comprising an antibody which binds to at least one of the proteins as defined in (1) to (3) of  claim 1 . 
     
     
         9 . A tester for determining the presence or absence of an antigen for an egg allergy in an object of interest, comprising a primer having a nucleotide sequence complementary to at least one of the nucleotide sequences set forth in SEQ ID NO: 1, 12, 17, 46, 58, 105, 151, 236, 250, or 261. 
     
     
         10 . A method for producing a processed product of an egg in which an antigen is eliminated or reduced, comprising the step of confirming that the antigen is eliminated or reduced in the process of producing the processed product, wherein the antigen is at least one of the proteins as defined in any of (1) to (3) of  claim 1 . 
     
     
         11 . An antigen derived from an egg, wherein the antigen is at least one of the proteins as defined in any of (1) to (3) of  claim 1  and causative of an egg allergy. 
     
     
         12 . A composition for diagnosing an egg allergy, the composition comprising, as an antigen, at least one of proteins as defined in any of (4) to (10) of  claim 2 . 
     
     
         13 . A method for providing an indicator for diagnosing an egg allergy in a subject, the method comprising the steps of:
 (i) contacting a sample obtained from the subject with an antigen, wherein the sample is a solution comprising an IgE antibody;   (ii) detecting binding between an IgE antibody present in the sample from the subject and the antigen; and   (iii) when the binding between the IgE antibody in the subject and the antigen is detected, an indicator of the fact that the subject is allergic to an egg is provided;   
       wherein the antigen is at least one of proteins as defined in any of (4) to (10) of  claim 2 . 
     
     
         14 . A pharmaceutical composition comprising at least one of the proteins as defined in (4) to (10) of  claim 2 . 
     
     
         15 . The pharmaceutical composition according to  claim 14 , wherein the pharmaceutical composition is intended for the treatment of an egg allergy. 
     
     
         16 . An egg, a processed product of an egg, or a bird which lays or has hatched from the egg in which an antigen is eliminated or reduced, wherein the antigen is at least one of the proteins as defined in (4) to (10) of  claim 2 . 
     
     
         17 . A tester for determining the presence or absence of an egg antigen in an object of interest, comprising an antibody which binds to at least one of the proteins as defined in (4) to (10) of  claim 2 . 
     
     
         18 . A method for producing a processed product of an egg in which an antigen is eliminated or reduced, comprising the step of confirming that the antigen is eliminated or reduced in the process of producing the processed product, wherein the antigen is at least one of the proteins as defined in any of (4) to (10) of  claim 2 . 
     
     
         19 . An antigen derived from an egg, wherein the antigen is at least one of the proteins as defined in any of (4) to (10) of  claim 2  and causative of an egg allergy.