Compositions and methods for modulating rsv infection and immunity

Abstract

Compositions and methods are provided for the treatment or prevention of RSV disease by modulating RSV infection and immunity. In particular, amino acid sequences in the RSV G glycoprotein, containing the chemokine motif defined as C-X-X-X-C (or CX3C), are identified that are essential in causing RSV infection and disease. The chemokine motif is biologically active and participates in virus binding to and infection of susceptible cells. The prevention or treatment of RSV infection is achieved by interfering with the motif, such as by administering a vaccine in which the motif is altered or by administration or induction of blocking molecules that inhibit the biological activity of the motif.

1 . A composition comprising a blocking molecule that inhibits the biological activity of a CX3C motif of a respiratory syncytial virus G glycoprotein, wherein C is a cysteine residue and X is any amino acid residue other than cysteine. 
     
     
         2 . The composition of  claim 1 , wherein the blocking molecule binds to the respiratory syncytial virus. 
     
     
         3 . The composition of  claim 1  wherein the CX3C motif is at amino acid positions 182-186 of a native respiratory syncytial virus G glycoprotein. 
     
     
         4 . The composition of  claim 1  wherein the blocking molecule is a drug, antibody, peptide, or polypeptide that binds to the CX3C motif of the RSV G glycoprotein. 
     
     
         5 . The composition of  claim 1  wherein the blocking molecule is a drug, antibody, peptide, or polypeptide that binds proximal to the CX3C motif and alters a secondary structure of the motif or sterically blocks respiratory syncytial virus G glycoprotein binding to a CX3C receptor or the biological activity associated with respiratory syncytial virus G glycoprotein binding to a CX3C receptor. 
     
     
         6 . The composition of  claim 1  wherein the blocking molecule is a drug, antibody, peptide, or polypeptide that binds to the CX3C receptor. 
     
     
         7 . The composition of  claim 1 , wherein the blocking agent is a peptide having the sequence TCAAACKRIPNKK (SEQ ID NO: 5). 
     
     
         8 . The composition of  claim 1 , wherein the blocking agent is a peptide having the sequence TCWAACKRIPNKK (SEQ ID NO: 6). 
     
     
         9 . The composition of  claim 1 , wherein the blocking agent is a peptide having the sequence TCNAACKRIPNKK (SEQ ID NO: 7). 
     
     
         10 . The composition of  claim 1 , wherein the blocking agent is a peptide having the sequence TCDAACKRIPNKK (SEQ ID NO: 8). 
     
     
         11 . The composition of  claim 1 , wherein the blocking agent is a peptide having the sequence TCHAACKRIPNKK (SEQ ID NO: 9). 
     
     
         12 . The composition of  claim 1 , wherein the blocking agent is a peptide having the sequence TCMAACKRIPNKK (SEQ ID NO: 10). 
     
     
         13 . The composition of  claim 1 , wherein the blocking agent is a peptide having the sequence TCFAACKRIPNKK (SEQ ID NO: 11). 
     
     
         14 . The composition of  claim 1 , wherein the blocking agent is a peptide having the sequence TCWAICKRIPNK (SEQ ID NO: 3). 
     
     
         15 . (canceled) 
     
     
         16 . The composition of  claim 1 , wherein the blocking agent is an antibody that binds to the peptide having the sequence TCWAICKRIPNK (SEQ ID NO: 3). 
     
     
         17 . (canceled) 
     
     
         18 . The composition of  claim 1  wherein the biological activity is chemotaxis, cell migration or virus adherence to cells. 
     
     
         19 - 34 . (canceled)