Stabilized soluble pre-fusion rsv f polypeptides

Abstract

Stable pre-fusion respiratory syncitial virus (RSV) F polypeptides, immunogenic compositions including the polypeptides, and uses thereof for the prevention and/or treatment of RSV infection are described.

What is claimed is: 
     
         1 . A vector comprising a nucleic acid molecule encoding a recombinant pre-fusion respiratory syncytial virus (RSV) Fusion (F) polypeptide, wherein the polypeptide comprises at least two stabilizing mutations in the F1 and/or F2 domain as compared to the RSV F1 and/or F2 domain in a wild-type RSV F protein, wherein at least one of the stabilizing mutations is a mutation of amino acid residue L on position 203 into I, wherein the F1 domain and the F2 domain are from an RSV B strain, and wherein the vector is an Ad26 vector. 
     
     
         2 . The vector according to  claim 1 , wherein the nucleic acid molecule has been codon-optimized for expression in mammalian cells. 
     
     
         3 . The vector according to  claim 1 , wherein the polypeptide further comprises a mutation of amino acid S on position 215 into P and/or a mutation of the amino acid residue D on position 486 into N. 
     
     
         4 . A composition comprising the vector according to  claim 1 . 
     
     
         5 . A method of inducing an immune response against RSV F protein in a subject, comprising administering to the subject the vector of  claim 1 . 
     
     
         6 . A method of vaccinating a subject against RSV comprising administering to the subject the vector of  claim 1 . 
     
     
         7 . A method of preventing and/or treating a RSV infection in a subject in need thereof, comprising administering to the subject the vector of  claim 1 . 
     
     
         8 . A pharmaceutical composition comprising the vector of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         9 . A method of inducing an immune response against RSV F protein in a subject, comprising administering to the subject the pharmaceutical composition of  claim 8 . 
     
     
         10 . A method of vaccinating a subject against RSV comprising administering to the subject the pharmaceutical composition of  claim 8 . 
     
     
         11 . A method of preventing and/or treating a RSV infection in a subject in need thereof, comprising administering to the subject the pharmaceutical composition of  claim 8 .