Vaccine against RSV
Compositions including a recombinant respiratory syncytial virus (RSV) Fusion (F) polypeptide that is stabilized in the pre-fusion conformation are described. The RSV F polypeptide includes at least one mutation as compared to a wild type RSV F polypeptide and the at least one mutation is a) a mutation of the amino acid aspartic acid (D) on position 486, b) a mutation of the amino acid aspartic acid (D) on position 489, or c) a mutation of the amino acid serine (S) on position 398 and/or the amino acid lysine (K) on position 394. Compositions including an isolated nucleic acid molecule encoding the stable RSV F polypeptides are also described.
1. An adenovirus type 26 (Ad26) vector comprising a nucleic acid encoding a recombinant respiratory syncytial virus (RSV) Fusion (F) polypeptide, wherein, as compared to a wild type RSV F polypeptide, the recombinant RSV F polypeptide comprises:
(i) a mutation of the amino acid at position 486 from aspartic acid (D) to asparagine (N),
(ii) at least one of
a. a mutation of the amino acid residue at position 67 from asparagine (N) or threonine (T) to isoleucine (I), and
b. a mutation of the amino acid residue at position 215 from serine (S) to proline (P), and
(iii) one or more additional mutations.
2. The Ad26 vector of claim 1 , wherein the recombinant RSV F polypeptide comprises at least one epitope that is recognized by a pre-fusion specific monoclonal antibody comprising a heavy chain variable region having a heavy chain complementary determining region (HCDR)1 of the amino acid sequence of SEQ ID NO: 4, a HCDR2 of the amino acid sequence of SEQ ID NO: 5, and a HCDR3 of the amino acid sequence of SEQ ID NO: 6, and a light chain variable region having a light chain complementary determining region (LCDR)1 of the amino acid sequence of SEQ ID NO: 7, a LCDR2 of the amino acid sequence of SEQ ID NO: 8, and a LCDR3 of the amino acid sequence of SEQ ID NO: 9.
3. The Ad26 vector according to claim 1 , wherein the recombinant RSV F polypeptide comprises:
(i) the mutation of the amino acid residue at position 486 from aspartic acid (D) to asparagine (N),
(ii) the mutation of the amino acid residue at position 67 from asparagine (N) or threonine (T) to isoleucine (I), and
(iii) the mutation of the amino acid residue at position 215 from serine (5) to proline (P).
4. The Ad26 vector according to claim 2 , wherein the pre-fusion specific monoclonal antibody comprises the heavy chain variable region having amino acids 1-125 of SEQ ID NO: 16, and the light chain variable region having amino acids 1-107 of SEQ ID NO: 17.
5. A composition comprising the Ad26 vector according to claim 1 and a pharmaceutically acceptable carrier.
6. A composition comprising the Ad26 vector according to claim 2 and a pharmaceutically acceptable carrier.
7. A composition comprising the Ad26 vector according to claim 3 and a pharmaceutically acceptable carrier.
8. A composition comprising the Ad26 vector according to claim 4 and a pharmaceutically acceptable carrier.
9. A method of inducing an immune response against RSV in a subject in need thereof, the method comprising administering to the subject a composition comprising the Ad26 vector according to claim 1 and a pharmaceutically acceptable carrier.
10. The method of claim 9 , wherein the composition is administered to the subject intramuscularly.
11. The method according to claim 9 , wherein the composition is administered to the subject more than once.
12. The method according to claim 9 , wherein the induced immune response comprises inducing neutralizing antibodies to RSV.
13. A method of inducing an immune response against RSV in a subject in need thereof, the method comprising administering to the subject a composition comprising the Ad26 vector according to claim 2 and a pharmaceutically acceptable carrier.
14. The method of claim 13 , wherein the composition is administered to the subject intramuscularly.
15. The method according to claim 13 , wherein the composition is administered to the subject more than once.
16. The method according to claim 13 , wherein the induced immune response comprises inducing neutralizing antibodies to RSV.
17. A method of inducing an immune response against RSV in a subject in need thereof, the method comprising administering to the subject a composition comprising the Ad26 vector according to claim 3 and a pharmaceutically acceptable carrier.
18. The method of claim 17 , wherein the composition is administered to the subject intramuscularly.
19. The method according to claim 17 , wherein the composition is administered to the subject more than once.
20. The method according to claim 17 , wherein the induced immune response comprises inducing neutralizing antibodies to RSV.