Method for the safe induction of immunity against RSV
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 1×10 10 to about 2×10 11 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 subject a composition comprising recombinant adenovirus comprising nucleic acid encoding an RSV Fusion (F) protein comprising the amino acid sequence of SEQ ID NO: 1, and a pharmaceutically acceptable carrier, 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 compositions comprises recombinant adenovirus comprising nucleic acid encoding an RSV Fusion (F) protein comprising the amino acid sequence of SEQ ID NO: 1, and a pharmaceutically acceptable carrier, in a total dose of 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 IFNy 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 adenovirus is of serotype 26 or 35.