Modified RSV F proteins and methods of their use
The present invention is generally related to modified or mutated respiratory syncytial virus fusion (F) proteins and methods for making and using them, including immunogenic compositions such as vaccines for the treatment and/or prevention of RSV infection.
1. A method of reducing respiratory syncytial virus (RSV) replication in the lung of an infant or juvenile, said method comprising:
administering an RSV Fusion (F) protein,
wherein the RSV F protein is encoded by a nucleic acid having the sequence of SEQ ID NO:7; and
wherein an immune response that reduces RSV replication in the lung is obtained.
2. The method of claim 1 , wherein the administration is intramuscular.
3. The method of claim 2 , wherein the immune response comprises neutralizing antibodies.
4. The method of claim 3 , wherein the neutralizing antibodies bind a polypeptide corresponding to amino acids 254-278 (SEQ ID NO:35) of the wild-type RSV F protein.
5. The method of claim 2 , wherein 1 microgram to 30 micrograms of the RSV F protein is administered.
6. The method of claim 2 , wherein 1 microgram to 10 micrograms of the RSV F protein is administered.
7. The method of claim 2 , wherein the RSV F protein is administered without an adjuvant.
8. The method of claim 2 , wherein the RSV F protein is administered with an adjuvant.
9. The method of claim 8 , wherein the adjuvant is alum.
10. The method of claim 2 , wherein the RSV F stimulated immune response is associated with reduced incidence of an RSV-induced pathological lung response compared to an immune response obtained by administering a formalin-inactivated RSV (FI-RSV).
11. The method of claim 10 , wherein the pathological lung response is selected from the group consisting of bronchiolitis, bronchitis, alveolitis, and pneumonitis.
12. The method of claim 1 further comprising administering one or more additional RSV proteins selected from the group consisting of an RSV M protein, and RSV N protein, and RSV G protein, and an RSV SH protein.
13. The method of claim 1 , wherein the RSV F protein consists of the amino acid sequence of SEQ ID NO:8.
14. The method of claim 1 , wherein the administration of the RSV F protein is a booster administration after an initial administration of the same antigen.
15. The method of claim 14 , wherein the booster administration is administered at about one month to about six months after the initial administration.
16. The method of claim 14 , wherein the booster administration is administered at six months after the initial administration.
17. The method of claim 1 wherein the RSV F protein lacks an N-terminal signal peptide.
18. The method of claim 1 wherein the RSV F protein is purified from an Sf9 insect host cell.