A fusion proteon of stromal cell-derived factor-1 (sdf-1) and interleukin-2 (il-2) and applications thereof

Abstract

The present invention provides a fusion protein, comprising a chemokine polypeptide, which is a chemokine or a receptor binding domain thereof; and a cytokine polypeptide connected to said chemokine polypeptide, which is an interleukin, a TNF-superfamily cytokine or a receptor-binding domain thereof; wherein the chemokine polypeptide and the cytokine polypeptide have a common target cell, and the fusion protein has an improved chemokine activity as compared to the chemokine polypeptide, and an improved cytokine activity as compared to the cytokine polypeptide.

1 . A method for promoting lymphocyte proliferation in a subject in need thereof, comprising administering to the subject a vaccine composition comprising a vaccine, in combination with a fusion protein of a stromal cell-derived factor-1 (SDF-1) and interleukin-2 (IL-2) as an adjuvant,
 wherein the SDF-1 has the amino acid sequence of SEQ ID NO: 10, 12, 14, 16 or 18, and the IL-2 has the amino acid sequence of SEQ ID NO: 30, 32, 34, 36 or 38, and the SDF-1 is connected to IL-2 by a hydrophilic helical peptide linker of (Glu-Ala-Ala-Ala-Lys) n  where n is less than 6,   wherein the vaccine composition is administered in an amount effective in inducing enhancement of lymphocyte proliferation compared with the vaccine alone.   
     
     
         2 . The method of  claim 1 , wherein the vaccine is a Newcastle Disease (ND) vaccine or an Avian Infectious Bronchitis (IB). 
     
     
         3 . The method of  claim 1 , wherein the fusion protein has the amino acid sequence of SEQ ID NO: 44. 
     
     
         4 . A method for promoting lymphocyte proliferation in a subject in need thereof, comprising administering to the subject a vaccine composition comprising a Newcastle Disease (ND) vaccine or an Avian Infectious Bronchitis (IB) vaccine, in combination with a fusion protein of a stromal cell-derived factor-1 (SDF-1) and interleukin-2 (IL-2) as an adjuvant, wherein the fusion protein has the amino acid sequence of SEQ ID NO: 44, and the vaccine composition is administered in an amount effective in inducing enhancement of lymphocyte proliferation compared with the ND vaccine or the IB vaccine alone. 
     
     
         5 . A method for promoting lymphocyte proliferation, comprising growing lymphocytes in a medium containing a fusion protein of a stromal cell-derived factor-1 (SDF-1) and interleukin-2 (IL-2) wherein the SDF-1 has the amino acid sequence of SEQ ID NO: 10, 12, 14, 16 or 18, and the IL-2 has the amino acid sequence of SEQ ID NO: 30, 32, 34, 36 or 38, and the SDF-1 is connected to IL-2 by a hydrophilic helical peptide linker of (Glu-Ala-Ala-Ala-Lys) n  where n is less than 6,
 wherein the fusion protein is present in the medium in an amount effective in inducing improvement of lymphocyte proliferation compared with the IL-2 alone.   
     
     
         6 . The method of  claim 4 , wherein the fusion protein has the amino acid sequence of SEQ ID NO: 44.