Method for the safe induction of immunity against rsv

Abstract

Methods of inducing a safe immune response against respiratory syncytial virus (RSV) in a human subject in need thereof, including administering to the subject a composition including recombinant adenovirus including a nucleic acid encoding an RSV Fusion (F) protein including the amino acid sequence of SEQ ID NO: 1, and a pharmaceutically acceptable carrier, in a total dose of from about 1×101° to about 2×10″ viral particles (vp), are described.

1 . A method of inducing a safe immune response against respiratory syncytial virus (RSV) in a human subject in need thereof, comprising administering to the human subject a composition comprising a replication-deficient recombinant adenovirus comprising a nucleic acid encoding an RSV Fusion (F) protein comprising the amino acid sequence of SEQ ID NO: 1, and a pharmaceutically acceptable carrier, wherein the recombinant adenovirus is administered in a total dose of from about 1×10 10  to about 2×10 11  viral particles (vp). 
     
     
         2 . The method according to  claim 1 , wherein the total dose is from about 5×10 10  to about 1×10 11  viral particles (vp). 
     
     
         3 . The method according to  claim 1 , wherein the immune response comprises the induction of antibodies specifically binding to RSV F protein. 
     
     
         4 . The method according to  claim 1 , wherein the immune response comprises the induction of RSV neutralizing antibodies. 
     
     
         5 . The method according to  claim 1 , wherein the immune response comprises the induction of antibodies specific for the RSV F protein in the pre-fusion conformation and antibodies specific for the RSV F protein in the post-fusion conformation, and wherein the geometric mean titer (GMT) increase of antibodies specific for RSV F protein in the pre-fusion conformation is higher than the geometric mean titer (GMT) increase of antibodies specific for RSV F protein in the post-fusion conformation, in enzyme linked immunosorbent assays (ELISAs). 
     
     
         6 . The method according to  claim 1 , wherein the ratio between the geometric mean titer (GMT) increase of post-fusion F specific antibodies as measured in ELISA and the geometric mean titer (GMT) increase of neutralizing antibodies as measured in a VNA assay is reduced after administration of said composition as compared to said ratio before administration of said composition. 
     
     
         7 . The method according to  claim 1 , wherein the immune response further comprises a cellular response as indicated by IFNgamma producing T cells as measured in an IFNγ ELISPOT in response to stimulation with a pool of peptides covering the RSV F protein of SEQ ID NO: 1, and/or by measurement of CD4 and CD8 T-cell subsets expressing IFNγ, IL-2 and TNFα by intracellular staining (ICS) after stimulation with a pool of peptides covering the RSV F protein of SEQ ID NO: 1. 
     
     
         8 . The method according to  claim 1 , wherein the subject is a human of 60 years or older. 
     
     
         9 . The method according to  claim 1 , wherein the nucleic acid encoding the RSV F protein comprises the nucleic acid sequence of SEQ ID NO: 2. 
     
     
         10 . The method according to  claim 1 , wherein the recombinant adenovirus is a human adenovirus. 
     
     
         11 . The method according to  claim 10 , wherein the recombinant adenovirus is of serotype 26 or 35. 
     
     
         12 . The method according to  claim 1 , wherein the composition is administered intranasally. 
     
     
         13 . The method according to  claim 1 , further comprising administering to the human subject the composition one year after the initial administration of the composition. 
     
     
         14 . A method of inducing a safe immune response against respiratory syncytial virus (RSV) in a human subject in need thereof, comprising administering to the human subject a composition comprising a replication-deficient recombinant adenovirus serotype 26 (Ad26) comprising the polynucleotide sequence of SEQ ID NO: 2, and a pharmaceutically acceptable carrier, wherein the recombinant Ad26 is administered in a total dose of from about 1×10 10  to about 2×10 11  viral particles (vp). 
     
     
         15 . The method according to  claim 14 , wherein the total dose is from about 5×10 10  to about 1×10 11  viral particles (vp). 
     
     
         16 . The method according to  claim 15 , wherein the composition is administered intranasally. 
     
     
         17 . The method according to  claim 14 , wherein the composition is administered intranasally. 
     
     
         18 . The method according to  claim 14 , wherein the subject is a human of 60 years or older. 
     
     
         19 . The method according to  claim 14 , further comprising administering to the human subject the composition one year after the initial administration of the composition. 
     
     
         20 . The method according to  claim 14 , wherein the immune response comprises the induction of RSV neutralizing antibodies.