Replikin peptides and antibodies therefor

Abstract

The present invention provides a new class of peptides related to rapid replication and their use in diagnosing, preventing and treating disease.

1 - 173 . (canceled) 
     
     
         174 . A method of making a virus vaccine comprising:
 identifying at least one Replikin sequence or at least one functional derivative fragment of said at least one Replikin sequence in at least one protein, polypeptide, or peptide of a virus, wherein said at least one Replikin sequence comprises 7 to 50 amino acid residues and comprises (1) at least one lysine residue six to ten amino acid residues from at least one other lysine residue, (2) at least one histidine residue, and (3) at least 6% lysine residues; and   making the virus vaccine comprising said at least one protein, polypeptide, or peptide of said virus.   
     
     
         175 . The method of  claim 174 , further comprising:
 isolating or synthesizing wherein said at least one protein, polypeptide, or peptide in which said at least one Replikin sequence or said at least one functional derivative fragment of said at least one Replikin sequence is identified, and   combining said at least one protein, polypeptide, or peptide with a pharmaceutically acceptable carrier and/or adjuvant to make said virus vaccine.   
     
     
         176 . The method of  claim 174 , wherein said at least one identified Replikin sequence is conserved in the virus for at least two consecutive years. 
     
     
         177 . The method of  claim 176 , wherein said virus is an influenza virus. 
     
     
         178 . The method of  claim 177 , wherein said at least one protein, polypeptide, or peptide is from a hemagglutinin protein. 
     
     
         179 . The method of making a virus vaccine of  claim 174 , wherein said at least one Replikin sequence consists of 7 to 50 amino acid residues. 
     
     
         180 . The method of making a virus vaccine of  claim 179 , wherein said at least one Replikin sequence has at least one lysine residue on one end of the sequence and at least one lysine residue or at least one histidine residue on the other end of the sequence. 
     
     
         181 . The method of making a virus vaccine of  claim 174 , wherein said at least one Replikin sequence or said at least one functional derivative fragment of said at least one Replikin sequence is said at least one Replikin sequence. 
     
     
         182 . A method of making a virus vaccine comprising:
 identifying at least one Replikin sequence or at least one functional derivative fragment of said at least one Replikin sequence in an amino acid sequence of a virus, wherein said at least one Replikin sequence comprises 7 to 50 amino acid residues and comprises (1) at least one lysine residue six to ten amino acid residues from at least one other lysine residue, (2) at least one histidine residue, and (3) at least 6% lysine residues, and   making the virus vaccine comprising said at least one Replikin sequence.   
     
     
         183 . The method of making a virus vaccine of  claim 182 , wherein said at least one Replikin sequence consists of 7 to 50 amino acids. 
     
     
         184 . The method of making a virus vaccine of  claim 183 , wherein said at least one Replikin sequence has at least one lysine residue on one end of the sequence and at least one lysine residue or at least one histidine residue on the other end of the sequence. 
     
     
         185 . The method of making a virus vaccine of  claim 182 , wherein said virus is an influenza virus. 
     
     
         186 . The method of making a virus vaccine of  claim 185 , wherein said amino acid sequence encodes an influenza protein. 
     
     
         187 . The method of making a virus vaccine of  claim 186  wherein said influenza protein is a hemagglutinin protein. 
     
     
         188 . The method of making a virus vaccine of  claim 182 , wherein said at least one Replikin sequence or said at least one functional derivative fragment of said at least one Replikin sequence is at least one Replikin sequence. 
     
     
         189 . A method of identifying an emerging strain of a virus comprising:
 obtaining at least one isolate of each strain of a plurality of strains of the virus;   analyzing an amino acid sequence of the at least one isolate of each strain of the plurality of strains of the virus for the presence and concentration of Replikin sequences, wherein a Replikin sequence is a peptide consisting of 7 to 50 amino acid residues with at least one lysine residue on one end of the peptide and at least one lysine residue or at least one histidine residue on the other end of the peptide comprising (1) at least one lysine residue six to ten amino acid residues from at least one other lysine residue, (2) at least one histidine residue, and (3) at least 6% lysine residues;   comparing the concentration of Replikin sequences in said amino acid sequence of said at least one isolate of each strain of the plurality of strains of the virus to the concentration of Replikin sequences observed in the amino acid sequence of each of the strains at least one earlier time period to provide the concentration of Replikin sequences for at least two time periods; and   identifying the strain of said virus having the highest increase in concentration of Replikin sequences between the at least two time periods as an emerging strain of the virus.   
     
     
         190 . The method of  claim 189 , wherein said virus is an influenza virus. 
     
     
         191 . The method of  claim 190 , wherein said amino acid sequence is the amino acid sequence of a protein of the influenza virus. 
     
     
         192 . The method of  claim 191 , wherein said protein of said influenza virus is a hemagglutinin protein or neuraminidase protein. 
     
     
         193 . A method of selecting a virus peptide for inclusion in a preventive or therapeutic virus vaccine comprising:
 selecting at least one Replikin sequence as a peptide for inclusion in a virus vaccine, wherein said at least one Replikin sequence is a Replikin sequence present in a virus identified as an emerging strain of virus in accordance with the method of  claim 189  and wherein said at least one Replikin sequence comprises 7 to 50 amino acid residues comprising (1) at least one lysine residue six to ten amino acid residues from at least one other lysine residue, (2) at least one histidine residue, and (3) at least 6% lysine residues.   
     
     
         194 . The method of selecting a virus peptide of  claim 193 , wherein said at least one Replikin sequence consists of 7 to 50 amino acid residues. 
     
     
         195 . The method of selecting a virus peptide of  claim 194 , wherein said at least one Replikin sequence has at least one lysine residue on one end of the sequence and at least one lysine residue or at least one histidine residue on the other end of the sequence. 
     
     
         196 . The method of  claim 193 , wherein the virus identified as an emerging strain of virus is an influenza virus. 
     
     
         197 . The method of  claim 196 , wherein said at least one Replikin sequence is identified in a hemagglutinin protein of said influenza virus. 
     
     
         198 . The method of  claim 193 , wherein said at least one Replikin sequence is conserved for at least two consecutive years within the strain of virus having the highest increase in Replikin sequence concentration between the at least two time periods. 
     
     
         199 . The method of  claim 193 , wherein a plurality of said at least one Replikin sequence is selected. 
     
     
         200 . A method of making a virus vaccine comprising:
 selecting at least one Replikin sequence present in an emerging strain of virus as a peptide template for virus vaccine manufacture, wherein said at least one Replikin sequence comprises 7 to 50 amino acids comprising (1) at least one lysine residue six to ten amino acid residues from at least one other lysine residue, (2) at least one histidine residue, and (3) at least 6% lysine residues;   synthesizing peptides having the amino acid sequence of the at least one selected Replikin sequence; and   combining the peptides with a pharmaceutically acceptable carrier and/or adjuvant to make a virus vaccine.   
     
     
         201 . The method of making a virus vaccine of  claim 200 , wherein said emerging strain of virus is identified by:
 obtaining at least one isolate of each strain of a plurality of strains of the virus;   analyzing an amino acid sequence of the at least one isolate of each strain of the plurality of strains of the virus for the presence and concentration of Replikin sequences, wherein a Replikin sequence is a peptide consisting of 7 to 50 amino acid residues with at least one lysine residue on one end of the peptide and at least one lysine residue or at least one histidine residue on the other end of the peptide comprising (1) at least one lysine residue six to ten amino acid residues from at least one other lysine residue, (2) at least one histidine residue, and (3) at least 6% lysine residues;   comparing the concentration of Replikin sequences in said amino acid sequence of said at least one isolate of each strain of the plurality of strains of the virus to the concentration of Replikin sequences observed in the amino acid sequence of each of the strains at least one earlier time period to provide the concentration of Replikin sequences for at least two time periods; and   identifying the strain of said virus having the highest increase in concentration of Replikin sequences between the at least two time periods as an emerging strain of the virus.   
     
     
         202 . The method of making a virus vaccine of  claim 200 , wherein said at least one Replikin sequence consists of 7 to 50 amino acids. 
     
     
         203 . The method of making a virus vaccine of  claim 202 , wherein said at least one Replikin sequence has at least one lysine residue on one end of the sequence and at least one lysine residue or at least one histidine residue on the other end of the sequence. 
     
     
         204 . The method of  claim 200 , wherein said at least one selected Replikin sequence is conserved in the virus for at least two consecutive years. 
     
     
         205 . The method of  claim 200 , wherein said virus is an influenza virus. 
     
     
         206 . The method of  claim 202 , wherein said virus is an influenza virus. 
     
     
         207 . The method of  claim 203 , wherein said virus is an influenza virus. 
     
     
         208 . The method of  claim 205 , wherein said at least one selected Replikin sequence is conserved in the hemagglutinin sequence of said influenza virus for at least two consecutive years. 
     
     
         209 . A virus vaccine comprising at least one isolated or synthesized Replikin sequence present in an emerging strain of virus, wherein said at least one isolated Replikin sequence comprises 7 to 50 amino acid residues comprising (1) at least one lysine residue six to ten amino acid residues from at least one other lysine residue, (2) at least one histidine residue, and (3) at least 6% lysine residues. 
     
     
         210 . The virus vaccine of  claim 209 , wherein said emerging strain of virus is identified by:
 obtaining at least one isolate of each strain of a plurality of strains of the virus;   analyzing an amino acid sequence of the at least one isolate of each strain of the plurality of strains of the virus for the presence and concentration of Replikin sequences, wherein a Replikin sequence is a peptide consisting of 7 to 50 amino acid residues with at least one lysine residue on one end of the peptide and at least one lysine residue or at least one histidine residue on the other end of the peptide comprising (1) at least one lysine residue six to ten amino acid residues from at least one other lysine residue, (2) at least one histidine residue, and (3) at least 6% lysine residues;   comparing the concentration of Replikin sequences in said amino acid sequence of said at least one isolate of each strain of the plurality of strains of the virus to the concentration of Replikin sequences observed in the amino acid sequence of each of the strains at least one earlier time period to provide the concentration of Replikin sequences for at least two time periods; and   identifying the strain of said virus having the highest increase in concentration of Replikin sequences between the at least two time periods as an emerging strain of the virus.   
     
     
         211 . The virus vaccine of  claim 209 , wherein said Replikin sequence consists of 7 to 50 amino acid residues. 
     
     
         212 . The virus vaccine of  claim 211 , wherein said Replikin sequence has at least one lysine residue on one end of the sequence and at least one lysine residue or at least one histidine residue on the other end of the sequence. 
     
     
         213 . The virus vaccine of  claim 209 , wherein said vaccine is an influenza virus vaccine and said at least one isolated Replikin sequence present in said emerging strain of virus is present in an emerging strain of influenza virus. 
     
     
         214 . The virus vaccine of  claim 209 , wherein said vaccine is an influenza virus vaccine and said at least one isolated Replikin sequence present in said emerging strain of virus is present in an emerging strain of influenza virus. 
     
     
         215 . The virus vaccine of  claim 212 , wherein said vaccine is an influenza virus vaccine and said at least one isolated Replikin sequence present in said emerging strain of virus is present in an emerging strain of influenza virus. 
     
     
         216 . The virus vaccine of  claim 209 , wherein the vaccine comprises a plurality of isolated Replikin sequences. 
     
     
         217 . The virus vaccine of  claim 209 , wherein the at least one isolated Replikin sequence is conserved for at least two consecutive years in the emerging strain. 
     
     
         218 . A method of preventing or treating virus infection comprising administering to a subject a vaccine comprising at least one isolated or synthesized Replikin sequence present in a strain of virus identified as an emerging strain, wherein said at least one isolated Replikin sequence comprises 7 to 50 amino acid residues comprising (1) at least one lysine residue six to ten amino acid residues from at least one other lysine residue, (2) at least one histidine residue, and (3) at least 6% lysine residues. 
     
     
         219 . The method of preventing or treating virus infection of  claim 218 , wherein said emerging strain of virus is identified by:
 obtaining at least one isolate of each strain of a plurality of strains of the virus;   analyzing an amino acid sequence of the at least one isolate of each strain of the plurality of strains of the virus for the presence and concentration of Replikin sequences, wherein a Replikin sequence is a peptide consisting of 7 to 50 amino acid residues with at least one lysine residue on one end of the peptide and at least one lysine residue or at least one histidine residue on the other end of the peptide comprising (1) at least one lysine residue six to ten amino acid residues from at least one other lysine residue, (2) at least one histidine residue, and (3) at least 6% lysine residues;   comparing the concentration of Replikin sequences in said amino acid sequence of said at least one isolate of each strain of the plurality of strains of the virus to the concentration of Replikin sequences observed in the amino acid sequence of each of the strains at least one earlier time period to provide the concentration of Replikin sequences for at least two time periods; and   identifying the strain of said virus having the highest increase in concentration of Replikin sequences between the at least two time periods as an emerging strain of the virus.   
     
     
         220 . The method of preventing or treating virus infection of  claim 218 , wherein said Replikin sequence consists of 7 to 50 amino acid residues. 
     
     
         221 . The method of preventing or treating virus infection of  claim 220 , wherein said Replikin sequence has at least one lysine residue on one end of the sequence and at least one lysine residue or at least one histidine residue on the other end of the sequence. 
     
     
         222 . The method of preventing or treating virus infection of  claim 218 , wherein said virus infection is an influenza virus infection. 
     
     
         223 . The method of preventing or treating virus infection of  claim 222 , wherein the vaccine is administered prior to the onset of influenza season. 
     
     
         224 . The method of preventing or treating virus infection of  claim 222 , further comprising administering an antiviral agent. 
     
     
         225 . The method of preventing or treating virus infection of  claim 224 , wherein the antiviral agent is gancyclovir. 
     
     
         226 . The method of preventing or treating virus infection of  claim 222 , wherein the vaccine comprises a Replikin sequence that has been conserved in said emerging strain of virus for at least about one year. 
     
     
         227 . A method of making a virus vaccine comprising:
 identifying at least one functional derivative of at least one Replikin sequence in at least one protein, polypeptide, or peptide of a virus, wherein said at least one Replikin sequence comprises 7 to 50 amino acid residues and comprises (1) at least one lysine residue six to ten amino acid residues from at least one other lysine residue, (2) at least one histidine residue, and (3) at least 6% lysine residues; and   making the virus vaccine comprising said at least one protein, polypeptide, or peptide of said virus.   
     
     
         228 . A method of making a virus vaccine comprising:
 identifying at least one functional derivative of at least one Replikin sequence in an amino acid sequence of a virus, wherein said at least one Replikin sequence comprises 7 to 50 amino acid residues and comprises (1) at least one lysine residue six to ten amino acid residues from at least one other lysine residue, (2) at least one histidine residue, and (3) at least 6% lysine residues; and   making the virus vaccine comprising said at least one functional derivative of said at least one Replikin sequence.   
     
     
         229 . The method of  claim 201 , wherein said at least one selected Replikin sequence is conserved in the virus for at least two consecutive years. 
     
     
         230 . The virus vaccine of  claim 210 , wherein said vaccine is an influenza virus vaccine and said at least one isolated Replikin sequence present in said emerging strain of virus is present in an emerging strain of influenza virus. 
     
     
         231 . The virus vaccine of  claim 210 , wherein said vaccine is an influenza virus vaccine and said at least one isolated Replikin sequence present in said emerging strain of virus is present in an emerging strain of influenza virus. 
     
     
         232 . The virus vaccine of  claim 210 , wherein the vaccine comprises a plurality of isolated Replikin sequences. 
     
     
         233 . The virus vaccine of  claim 210 , wherein the at least one isolated Replikin sequence is conserved for at least two consecutive years in the emerging strain.